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4-Methylmorpholine → 1-[(R)-Isopropoxycarbonylamino-phenyl-acetyl]-pyrrolidine-2-(S)-carboxylic acid methyl ester

HRID 1008559
Notes
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Reaction equation

HRID 1008559 reaction equation
[CH:1]([O:4][C:5]([NH:7][C@H:8]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:9]([OH:11])=O)=[O:6])([CH3:3])[CH3:2].Cl.[CH3:19][O:20][C:21](=[O:27])[C@@H:22]1[CH2:26][CH2:25][CH2:24][NH:23]1.CN1CCOCC1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C)C=O.O>[CH3:19][O:20][C:21]([C@@H:22]1[CH2:26][CH2:25][CH2:24][N:23]1[C:9](=[O:11])[C@H:8]([NH:7][C:5]([O:4][CH:1]([CH3:2])[CH3:3])=[O:6])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:27]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 2733200methyl L-prolinate hydrochlorideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 53741285(R)-Isopropoxycarbonylamino-phenyl-acetic acid

Product 1

HCID 545024061-[(R)-Isopropoxycarbonylamino-phenyl-acetyl]-pyrrolidine-2-(S)-carboxylic acid methyl ester
Yield 91%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of (R)-Isopropoxycarbonylamino-phenyl-acetic acid (0.74 g), (L)-proline methyl ester hydrochloride (0.51 g), N-methyl morpholine (1.00 mL) and 1.00 g of 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) in 10 mL of dry N,N-dimethyl formamide was stirred for 3 h at ambient temperature. The volatiles were pumped off and water was added followed by extraction with ethyl acetate and concentration of the organic layer. The remaining residue was purified by silica chromatography (ethyl acetate/isohexane=3/1) to give 0.95 g (91%) of the title compound as a colorless oil. (+)-APCI-MS: 349 (MH+).

Workup

  1. extractionfollowed by extraction with ethyl acetate and concentration of the organic layer
  2. customThe remaining residue was purified by silica chromatography (ethyl acetate/isohexane=3/1)

Sources & evidence

ORD record
ord-1a783f7d90074c9aabc9cd6471b5caa3
Source dataset
uspto-grants-2004_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06797710B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes