Sodium borohydride → 3-(4-Chloro-benzyl)-azetidine-1-carboxylic acid tert-butyl ester

HRID 1182098Notes

Reaction equation

HRID 1182098 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([CH:12]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)I)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>CS(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([CH2:12][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 693587933-[(4-Chloro-phenyl)-iodo-methyl]-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 693583843-(4-Chloro-benzyl)-azetidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 3-[(4-Chloro-phenyl)-iodo-methyl]-azetidine-1-carboxylic acid tert-butyl ester (58 g, 140 mmol) in dimethylsulphoxide (450 ml) is treated with sodium borohydride with cooling. The reaction mixture was stirred at room temperature for 20 hours, then quenched by the slow addition of water (1000 ml). The aqueous mixture is extracted into ethylacetate, and the ethylacetate phase washed with saturated brine, dried over magnesium sulphate and evaporated. The crude product is purified by flash chromatography using a biotage 75 column (eluant gradient isohexane:ethylacetate 9:1 to 85:15) to afford 3-(4-Chloro-benzyl)-azetidine-1-carboxylic acid tert-butyl ester. 1H NMR 400 MHz, CDCl3, δ 1.35 (9H), 2.70 (1H), 2.80 (2H), 3.55 (2H), 3.90 (2H), 6.97 (2H), 7.17 (2H).

Workup

  1. temperaturewith cooling
  2. customquenched by the slow addition of water (1000 ml)
  3. extractionThe aqueous mixture is extracted into ethylacetate
  4. washthe ethylacetate phase washed with saturated brine
  5. dry with materialdried over magnesium sulphate
  6. customevaporated
  7. customThe crude product is purified by flash chromatography

Sources & evidence

ORD record
ord-351c1662bfd34910b70ec4ca8300d864
Source dataset
uspto-grants-2007_10
Patent number
US07288537B2

Reaction notes

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