Ethyl chloroformate → (S)-tert-Butyl 2-((3-(3,4-dimethoxyphenoxy)-2-oxopropyl)carbamoyl)pyrrolidine-1-carboxylate

HRID 710063Notes

Reaction equation

HRID 710063 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(OCC)=O.Cl.[NH2:23][CH2:24][C:25](=[O:38])[CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([O:36][CH3:37])[CH:29]=1>O.C1COCC1.CCN(CC)CC>[CH3:37][O:36][C:30]1[CH:29]=[C:28]([CH:33]=[CH:32][C:31]=1[O:34][CH3:35])[O:27][CH2:26][C:25](=[O:38])[CH2:24][NH:23][C:13]([C@@H:9]1[CH2:10][CH2:11][CH2:12][N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:15]

Participants

7

Reactant 3

HCID 10928Ethyl chloroformateHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 867067751-Amino-3-(3,4-dimethoxyphenoxy)propan-2-one hydrochloride

Product 1

HCID 86706777(S)-tert-Butyl 2-((3-(3,4-dimethoxyphenoxy)-2-oxopropyl)carbamoyl)pyrrolidine-1-carboxylateYield 49.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a THF (14 ml) solution of (S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (0.557 g) and Et3N (0.790 ml), ethyl chloroformate (0.295 g) was added over an ice bath, followed by stirring at the same temperature for 30 minutes. The reaction mixture was added at 0° C. to a THF (7 ml) solution of the compound (0.701 g) obtained in Example 19-(3) and the mixture was stirred at room temperature for 17 hours. After adding water and performing extraction with AcOEt, the organic layer was washed with saturated aqueous sodium chloride, dried (MgSO4), filtered and concentrated to give a crude product, which was further purified by silica gel chromatography (AcOEt/hexane) to give the titled compound (0.540 g, brown amorphous.)

Workup

  1. stirringthe mixture was stirred at room temperature for 17 hours
  2. extractionextraction with AcOEt
  3. washthe organic layer was washed with saturated aqueous sodium chloride
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a crude product, which
  8. customwas further purified by silica gel chromatography (AcOEt/hexane)

Sources & evidence

ORD record
ord-b5816afde8eb491888adea536c4c062a
Source dataset
uspto-grants-2015_11
Patent number
US09181229B2

Reaction notes

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