Dimethylformamide → (2S,4S)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester

HRID 1481916Notes

Reaction equation

HRID 1481916 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([NH:13][C:14]([O:16][CH2:17][CH:18]2[C:30]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:24]3[C:19]2=[CH:20][CH:21]=[CH:22][CH:23]=3)=[O:15])[CH2:10][C@H:9]1[C:31]([OH:33])=[O:32])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C.Br[CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>CO.O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([NH:13][C:14]([O:16][CH2:17][CH:18]2[C:30]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:24]3[C:19]2=[CH:20][CH:21]=[CH:22][CH:23]=3)=[O:15])[CH2:10][C@H:9]1[C:31]([O:33][CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:32])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 2756134(4S)-4-N-Fmoc-amino-1-Boc-L-proline

Product 1

HCID 68283347(2S,4S)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl esterYield 77%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

To a suspension of (2S,4S)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (Aldrich) (1 g, 2.21 mmol) in methanol (6 mL) was added a solution potassium carbonate (153 mg, 1.1 mmol) in water (6 mL) dropwise. The mixture was stirred at room temperature for 1 hour, concentrated, and the residue slurried in toluene and evaporated to dryness 3 times and once from diethyl ether to give a white solid. The solid was mixed with DMF (6 mL), and bromomethyl-benzene (289 μL, 2.43 mmol) was added dropwise at room temperature. After 16 hours the mixture was diluted with water extracted with ethyl acetate. The combined extracts were washed with water, brine and dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel chromatography to give (2S,4S)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester (0.92 g, 77%) as a foam.

Workup

  1. concentrationconcentrated
  2. customevaporated to dryness 3 times and once from diethyl ether
  3. customto give a white solid
  4. additionwas added dropwise at room temperature
  5. extractionextracted with ethyl acetate
  6. washThe combined extracts were washed with water, brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-5a59d577ca0243af8fc3c47303f6ce57
Source dataset
uspto-grants-2016_08
Patent number
US09409888B2

Reaction notes

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