Sodium hydride → 3-(4-Chloro-benzyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 584645Notes

Reaction equation

HRID 584645 reaction equation
C([CH:5]1[CH:9]([OH:10])[CH2:8][CH2:7][N:6]1[C:11]([OH:13])=[O:12])(C)(C)C.[H-].[Na+].[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21]Br)=[CH:19][CH:18]=1>C1COCC1>[C:20]([O:13][C:11]([N:6]1[CH2:7][CH2:8][CH:9]([O:10][CH2:21][C:20]2[CH:23]=[CH:24][C:17]([Cl:16])=[CH:18][CH:19]=2)[CH2:5]1)=[O:12])([CH3:23])([CH3:21])[CH3:19]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 22313762Tert-butyl 3-hydroxy-1-pyrrolidinecarboxylic acid

Product 1

HCID 667576123-(4-Chloro-benzyloxy)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 110.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of tert-butyl 3-hydroxy-1-pyrrolidinecarboxylic acid (0.27 g, 1.44 mmol) in dry THF (4 mL) was added dropwise to a cold (0° C.), stirred suspension of sodium hydride (0.078 g, 2.17 mmol, ca. 50% suspension in oil) in THF (10 mL). After 30 min. a solution of 4-chlorobenzyl bromide (0.36 g, 1.74 mmol) in THF (2 mL) was added and the resulting suspension was stirred at R.T. overnight. The reaction mixture was partitioned between water and ethyl acetate. The aqueous phase was extracted with ethyl acetate and the combined organic phase was washed with saturated aqueous sodium chloride, dried and concentrated. The residue was subjected to flash chromatography (heptane-ethyl acetate, 6:1) to afford the subtitle compound 3-(4-Chloro-benzyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester as an oil (0.30 g, 66.8%).

Workup

  1. stirringthe resulting suspension was stirred at R.T. overnight
  2. customThe reaction mixture was partitioned between water and ethyl acetate
  3. extractionThe aqueous phase was extracted with ethyl acetate
  4. washthe combined organic phase was washed with saturated aqueous sodium chloride
  5. customdried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-b417093e1c80410392982d5f408437b6
Source dataset
uspto-grants-2005_08
Patent number
US06927222B2

Reaction notes

Loading…