L-Threonine → methyl 4-[(3R,4S)-3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]-3,5-difluorobenzoate

HRID 732694Notes

Reaction equation

HRID 732694 reaction equation
[C:1]1([C@H:11]([N:13]([CH2:21][C@@H:22]2[C@@H:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:25][NH:24][CH2:23]2)[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].[F:39][C:40]1[CH:41]=[C:42]([CH:47]=[C:48]([F:51])[C:49]=1F)[C:43]([O:45][CH3:46])=[O:44].N[C@H](C(O)=O)[C@@H](C)O>C(OCC)(=O)C.CS(C)=O>[C:16]([O:15][C:14]([N:13]([CH2:21][C@@H:22]1[C@@H:26]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:25][N:24]([C:49]2[C:48]([F:51])=[CH:47][C:42]([C:43]([O:45][CH3:46])=[O:44])=[CH:41][C:40]=2[F:39])[CH2:23]1)[C@@H:11]([C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1)[CH3:12])=[O:20])([CH3:18])([CH3:19])[CH3:17]

Participants

7

Reactant 4

HCID 6288L-ThreonineHCID 11430Potassium CarbonateHCID 2783211Methyl 3,4,5-trifluorobenzoateHCID 86628525tert-butyl [(1R)-1-(1-naphthyl)ethyl]{[(3R,4S)-4-phenylpyrrolidin-3-yl]methyl}carbamate

Product 1

HCID 68915177methyl 4-[(3R,4S)-3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]-3,5-difluorobenzoate

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A 10 ml DMSO solution of tert-butyl [(1R)-1-(1-naphthyl)ethyl]{[(3R,4S)-4-phenylpyrrolidin-3-yl]methyl}carbamate was mixed with 1.3 g of potassium carbonate and 1.0 g of methyl 3,4,5-trifluorobenzoate and stirred overnight at 110° C. Thr reaction solution was mixed with ethyl acetate, washed with water and dried with anhydrous sodium sulfate. This was concentrated under a reduced pressure, and the thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate) to obtain 2.1 g of methyl 4-[(3R,4S)-3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-phenylpyrrolidin-1-yl]-3,5-difluorobenzoate as a colorless amorphous substance.

Workup

  1. washwashed with water
  2. dry with materialdried with anhydrous sodium sulfate
  3. concentrationThis was concentrated under a reduced pressure
  4. customthe thus obtained residue was purified by a silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-a510ec91c6224ea39e4bb0083b0cd018
Source dataset
uspto-grants-2009_09
Patent number
US07585886B2

Reaction notes

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