83249-10-9 (双环[1.1.1]戊烷-1,3-二甲酸单甲酯,3-Methoxycarbonylbicyclo[1.1.1]pentane-1-carboxylic acid)

反应条件：

1.1 Reagents: Lithium hydroxide Solvents: Tetrahydrofuran ; 72 h, 50 °C; 50 °C → rt
1.2 Reagents: Hydrochloric acid Solvents: Water ; pH 3 - 4, rt

参考文献：

Large-scale synthesis and modifications of bicyclo[1.1.1]pentane-1,3-dicarboxylic acid (BCP)

Ripenko, Vasyl; et al, Journal of Organic Chemistry, 2021, 86(20), 14061-14068

合成路线：1 步

115913-32-1

_88%

反应条件：

1.1 Reagents: Sodium hydroxide

参考文献：

Bicyclo[1.1.1]pentane-Derived Building Blocks for Click Chemistry

Kokhan, Serhii O.; et al, European Journal of Organic Chemistry, 2017, 2017(43), 6450-6456

合成路线：1 步

115913-32-1

_75%

反应条件：

1.1 Reagents: Sodium hydroxide Solvents: Methanol ; 10 min, 23 °C; 1 h, reflux
1.2 Reagents: Hydrochloric acid Solvents: Water ; pH 2

参考文献：

Application of the Bicyclo[1.1.1]pentane Motif as a Nonclassical Phenyl Ring Bioisostere in the Design of a Potent and Orally Active γ-Secretase Inhibitor

Stepan, Antonia F.; et al, Journal of Medicinal Chemistry, 2012, 55(7), 3414-3424

合成路线：1 步

83249-09-6

_49%

反应条件：

1.1 Reagents: Sodium periodate Catalysts: Ruthenium trichloride Solvents: Carbon tetrachloride , Acetonitrile , Water ; 96 h

参考文献：

3-aminobicyclo[1.1.1]pentane-1-carboxylic acid derivatives: Synthesis and incorporation into peptides

Paetzel, Michael; et al, European Journal of Organic Chemistry, 2004, (3), 493-498

合成路线：1 步

_40%

参考文献：

3-Carboxy-/3-Aminobicyclo[1.1.1]pentane-Derived Sulfonamides and Sulfonyl Fluorides - Advanced Bifunctional Reagents for Organic Synthesis and Drug Discovery

Kokhan, Serhii O.; et al, European Journal of Organic Chemistry, 2020, 2020(15), 2210-2216

合成路线：1 步

参考文献：

Synthesis and Biopharmaceutical Evaluation of Imatinib Analogues Featuring Unusual Structural Motifs

Nicolaou, Kyriacos C.; et al, ChemMedChem, 2016, 11(1), 31-37

合成路线：2 步

56842-95-6

67-56-1

反应条件：

1.1 Reagents: Thionyl chloride Solvents: Methanol ; 20 - 40 °C; overnight, rt
2.1 Reagents: Lithium hydroxide Solvents: Tetrahydrofuran ; 72 h, 50 °C; 50 °C → rt
2.2 Reagents: Hydrochloric acid Solvents: Water ; pH 3 - 4, rt

参考文献：

Large-scale synthesis and modifications of bicyclo[1.1.1]pentane-1,3-dicarboxylic acid (BCP)

Ripenko, Vasyl; et al, Journal of Organic Chemistry, 2021, 86(20), 14061-14068

合成路线：2 步

反应条件：

1.1 Reagents: Methyllithium Solvents: Diethyl ether ; -30 °C
1.2 Solvents: Diethyl ether ; 0 °C; 4 d, rt
1.3 Solvents: Diethoxymethane ; 5 h; 12 h, rt
1.4 Reagents: Hydrochloric acid Solvents: Water
2.1 Reagents: Sodium periodate Catalysts: Ruthenium trichloride Solvents: Carbon tetrachloride , Acetonitrile , Water ; 96 h

参考文献：

3-aminobicyclo[1.1.1]pentane-1-carboxylic acid derivatives: Synthesis and incorporation into peptides

Paetzel, Michael; et al, European Journal of Organic Chemistry, 2004, (3), 493-498

合成路线：2 步

67-56-1

反应条件：

1.1 Reagents: Sodium hydroxide , Bromine Solvents: 1,4-Dioxane , Water
1.2 Reagents: Thionyl chloride Solvents: Thionyl chloride
1.3 Solvents: Methanol
2.1 Reagents: Sodium hydroxide Solvents: Methanol

参考文献：

(S)-(+)-2-(3'-Carboxybicyclo[1.1.1]pentyl)- glycine, a Structurally New Group I Metabotropic Glutamate Receptor Antagonist

Pellicciari, Roberto; et al, Journal of Medicinal Chemistry, 1996, 39(15), 2874-2876

合成路线：2 步

115913-31-0

67-56-1

反应条件：

1.1 Solvents: Methanol
2.1 Reagents: Sodium hydroxide Solvents: Methanol

参考文献：

A practical photochemical synthesis of bicyclo[1.1.1]pentane-1,3-dicarboxylic acid

Kaszynski, Piotr; et al, Journal of Organic Chemistry, 1988, 53(19), 4593-4

合成路线：3 步

反应条件：

1.1 Reagents: Sodium hydroxide , Bromine Solvents: Water ; 20 °C; 3 h, 20 °C; 20 °C → 0 °C
1.2 Solvents: 1,4-Dioxane ; 0 °C; overnight, 0 °C
2.1 Reagents: Thionyl chloride Solvents: Methanol ; 20 - 40 °C; overnight, rt
3.1 Reagents: Lithium hydroxide Solvents: Tetrahydrofuran ; 72 h, 50 °C; 50 °C → rt
3.2 Reagents: Hydrochloric acid Solvents: Water ; pH 3 - 4, rt

参考文献：

Large-scale synthesis and modifications of bicyclo[1.1.1]pentane-1,3-dicarboxylic acid (BCP)

Ripenko, Vasyl; et al, Journal of Organic Chemistry, 2021, 86(20), 14061-14068

合成路线：3 步

反应条件：

1.1 Reagents: Sodium hydroxide , Bromine
1.2 Reagents: Hydrochloric acid Solvents: Water
2.1 Reagents: Thionyl chloride
2.2 -
3.1 Reagents: Sodium hydroxide

参考文献：

Bicyclo[1.1.1]pentane-Derived Building Blocks for Click Chemistry

Kokhan, Serhii O.; et al, European Journal of Organic Chemistry, 2017, 2017(43), 6450-6456

合成路线：3 步

反应条件：

1.1 Reagents: Sodium hydroxide , Bromine Solvents: 1,4-Dioxane , Water ; 4 min, 23 °C → 27 °C; 27 °C → -10 °C; 45 min, -10 °C; -3 °C → 3 °C; 13 h, 3 °C → 23 °C
1.2 Reagents: Sodium bisulfite ; 25 min, 23 °C
1.3 Reagents: Hydrochloric acid Solvents: Water ; pH 2
2.1 Reagents: Thionyl chloride ; 12 h, reflux; reflux → 23 °C; 23 °C → 0 °C
2.2 0 °C → 40 °C; 1 h, reflux
3.1 Reagents: Sodium hydroxide Solvents: Methanol ; 10 min, 23 °C; 1 h, reflux
3.2 Reagents: Hydrochloric acid Solvents: Water ; pH 2

参考文献：

Application of the Bicyclo[1.1.1]pentane Motif as a Nonclassical Phenyl Ring Bioisostere in the Design of a Potent and Orally Active γ-Secretase Inhibitor

Stepan, Antonia F.; et al, Journal of Medicinal Chemistry, 2012, 55(7), 3414-3424

合成路线：3 步

431-03-8

反应条件：

1.1 Reagents: Methyllithium Solvents: Diethyl ether , Pentane
1.2 Solvents: Diethyl ether , Pentane
2.1 Reagents: Sodium hydroxide , Bromine Solvents: 1,4-Dioxane , Water
2.2 Reagents: Thionyl chloride Solvents: Thionyl chloride
2.3 Solvents: Methanol
3.1 Reagents: Sodium hydroxide Solvents: Methanol

参考文献：

(S)-(+)-2-(3'-Carboxybicyclo[1.1.1]pentyl)- glycine, a Structurally New Group I Metabotropic Glutamate Receptor Antagonist

Pellicciari, Roberto; et al, Journal of Medicinal Chemistry, 1996, 39(15), 2874-2876

合成路线：4 步

431-03-8

反应条件：

1.1 Reagents: Methyllithium Solvents: Diethyl ether , Pentane ; 60 min, -78 °C; 15 min, -78 °C; 1 h, 0 °C
1.2 Solvents: Diethyl ether , Pentane ; 0 °C → -10 °C; -10 °C → -5 °C; -5 °C → 5 °C
2.1 Reagents: Sodium hydroxide , Bromine Solvents: 1,4-Dioxane , Water ; 4 min, 23 °C → 27 °C; 27 °C → -10 °C; 45 min, -10 °C; -3 °C → 3 °C; 13 h, 3 °C → 23 °C
2.2 Reagents: Sodium bisulfite ; 25 min, 23 °C
2.3 Reagents: Hydrochloric acid Solvents: Water ; pH 2
3.1 Reagents: Thionyl chloride ; 12 h, reflux; reflux → 23 °C; 23 °C → 0 °C
3.2 0 °C → 40 °C; 1 h, reflux
4.1 Reagents: Sodium hydroxide Solvents: Methanol ; 10 min, 23 °C; 1 h, reflux
4.2 Reagents: Hydrochloric acid Solvents: Water ; pH 2

参考文献：

Application of the Bicyclo[1.1.1]pentane Motif as a Nonclassical Phenyl Ring Bioisostere in the Design of a Potent and Orally Active γ-Secretase Inhibitor

Stepan, Antonia F.; et al, Journal of Medicinal Chemistry, 2012, 55(7), 3414-3424

合成路线：3 步

56842-95-6

反应条件：

1.1 Reagents: Thionyl chloride Solvents: Thionyl chloride
2.1 Solvents: Methanol
3.1 Reagents: Sodium hydroxide Solvents: Methanol

参考文献：

A practical photochemical synthesis of bicyclo[1.1.1]pentane-1,3-dicarboxylic acid

Kaszynski, Piotr; et al, Journal of Organic Chemistry, 1988, 53(19), 4593-4

合成路线：4 步

105542-93-6

反应条件：

1.1 Reagents: Sodium hypobromite Solvents: 1,4-Dioxane , Water
2.1 Reagents: Thionyl chloride Solvents: Thionyl chloride
3.1 Solvents: Methanol
4.1 Reagents: Sodium hydroxide Solvents: Methanol

参考文献：

A practical photochemical synthesis of bicyclo[1.1.1]pentane-1,3-dicarboxylic acid

Kaszynski, Piotr; et al, Journal of Organic Chemistry, 1988, 53(19), 4593-4

合成路线：4 步

35634-10-7

123-54-6

反应条件：

1.1 -
2.1 Reagents: Sodium hydroxide , Bromine
2.2 Reagents: Hydrochloric acid Solvents: Water
3.1 Reagents: Thionyl chloride
3.2 -
4.1 Reagents: Sodium hydroxide

参考文献：

Bicyclo[1.1.1]pentane-Derived Building Blocks for Click Chemistry

Kokhan, Serhii O.; et al, European Journal of Organic Chemistry, 2017, 2017(43), 6450-6456

合成路线：4 步

123-54-6

反应条件：

1.1 Reagents: Methyllithium Solvents: Diethyl ether
1.2 -
2.1 Reagents: Sodium hydroxide , Bromine
2.2 Reagents: Hydrochloric acid Solvents: Water
3.1 Reagents: Thionyl chloride
3.2 -
4.1 Reagents: Sodium hydroxide

参考文献：

Bicyclo[1.1.1]pentane-Derived Building Blocks for Click Chemistry

Kokhan, Serhii O.; et al, European Journal of Organic Chemistry, 2017, 2017(43), 6450-6456

合成路线：4 步

1871-57-4

75-25-2