Water → HCID 70976012, compound

HRID 455250Notes

Reaction equation

HRID 455250 reaction equation
C(N(C(C)C)CC)(C)C.[CH3:10][O:11][C:12]([C@@H:14]1[CH2:18][C@@H:17]([OH:19])[CH2:16][NH:15]1)=[O:13].[N:20]([C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=1)=[C:21]=[O:22].O>ClCCl>[CH3:10][O:11][C:12]([C@@H:14]1[CH2:18][C@@H:17]([OH:19])[CH2:16][N:15]1[C:21](=[O:22])[NH:20][C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]([F:31])([F:33])[F:32])=[CH:25][CH:24]=1)=[O:13]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 92298p-(Trifluoromethoxy)phenyl isocyanateHCID 7015125(4R)-4-Hydroxy-L-proline methyl ester

Product 1

HCID 70976012HCID 70976012, compoundYield 97.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diisopropylethylamine (0.782 g, 5.5 mmol) was dropped into a suspension of compound (2S,4R)-4-Hydroxy-pyrrolidine-2-carboxylic acid methyl ester (1.0 g, 5.5 mmol) in anhydrous dichloromethane (50 mL), the mixture was stirred at room temperature for 10 minutes. 1-isocyanato-4-(trifluoromethoxy)benzene (1.116 g, 5.5 mmol) was added to the suspension and the mixture was continued to be stirred for 2 hours at room temperature. The mixture was poured into water (50 mL), the resulting mixture was filtrated. The liquid was extracted with dichloromethane (3×50 mL). The organic layers was combined, washed with brine (50 mL), dried over anhydrous sodium sulphate, filtered and concentrated. The residue combined with the filter cake yielded 1.86 g (97%) of the target compound. 1H NMR (300 MHz, CDCl3): δ 7.41 (d, 2H, J=9.0 Hz), 7.14 (d, 2H, J=8.7 Hz), 6.59 (s, 1H), 4.64 (t, 2H, J=7.5 Hz), 3.78-3.73, (m, 4H), 3.59 (d, 1H, J=9.9 Hz), 2.36-2.21 (m, 2H); LC-MS: 349.1 [M+1]+.

Workup

  1. stirringto be stirred for 2 hours at room temperature
  2. filtrationthe resulting mixture was filtrated
  3. extractionThe liquid was extracted with dichloromethane (3×50 mL)
  4. washwashed with brine (50 mL)
  5. dry with materialdried over anhydrous sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-1bcda22aa2674ab6a6e556856f5592e5
Source dataset
uspto-grants-2013_07
Patent number
US08497288B2

Reaction notes

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