2,4-Dichlorobenzylamine → 3-(2,4-Dichlorobenzylamino)-4-fluoropyrrolidine-1-carboxylic acid tert-butyl ester

HRID 252092Notes

Reaction equation

HRID 252092 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:15]([O:19][C:20]([N:22]1[CH2:26][C:25](=O)[CH:24]([F:28])[CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].[Cl:29][C:30]1[CH:37]=[C:36]([Cl:38])[CH:35]=[CH:34][C:31]=1[CH2:32][NH2:33].[OH-].[Na+]>ClCCCl.C(O)(=O)C>[C:15]([O:19][C:20]([N:22]1[CH2:23][CH:24]([F:28])[CH:25]([NH:33][CH2:32][C:31]2[CH:34]=[CH:35][C:36]([Cl:38])=[CH:37][C:30]=2[Cl:29])[CH2:26]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]

Participants

7

Reactant 4

HCID 14852,4-DichlorobenzylamineHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 451589161-Boc-3-fluoro-4-pyrrolidinone

Product 1

HCID 668552813-(2,4-Dichlorobenzylamino)-4-fluoropyrrolidine-1-carboxylic acid tert-butyl esterYield 22%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 111,2-DichloroethaneSolvent

Procedure

Add sodium triacetoxyborohydride (156 mg, 0.73 mmol) to a mixture of 3-fluoro-4-oxopyrrolidine-1-carboxylic acid tert-butyl ester (100 mg, 0.5 mmol) and 2,4-dichlorobenzylamine (65 μL, 0.5 mmol) in 1,2-dichloroethane (1.5 mL), followed by 2 drops of glacial acetic acid and stir overnight at room temperature. Pour the crude mixture into 2 N sodium hydroxide and extract with ethyl acetate, wash with water, dry (magnesium sulfate), concentrate and chromatograph on silica gel to give 3-(2,4-dichlorobenzylamino)-4-fluoropyrrolidine-1-carboxylic acid tert-butyl ester (40 mg, 20%). 1H NMR (300 MHz, CDCl3) δ 7.36-7.44 (2H, m), 7.20-7.28 (1H, m), 5.03 (1H, d, J=54.07 Hz), 3.21-3.95 (6H, m), 2.99-3.15 (1H, m), 1.45 (9H, s), MS (ES): m/z=363 [M+].

Workup

  1. extractionextract with ethyl acetate
  2. washwash with water
  3. dry with materialdry (magnesium sulfate)
  4. concentrationconcentrate

Sources & evidence

ORD record
ord-a6025a001bb043d487d4aa746b98fe5c
Source dataset
uspto-grants-2011_01
Patent number
US07868014B2

Reaction notes

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