Cesium carbonate → (3S)-N-(5-chloro-2-[(2S)-oxiran-2-ylmethoxy]phenyl}-3-hydroxypyrrolidine-1-carboxamide

HRID 270114Notes

Reaction equation

HRID 270114 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:17])=[C:6]([NH:8][C:9]([N:11]2[CH2:15][CH2:14][C@H:13]([OH:16])[CH2:12]2)=[O:10])[CH:7]=1.[N+](C1C=C(S(O[CH2:31][C@@H:32]2[CH2:34][O:33]2)(=O)=O)C=CC=1)([O-])=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:17][CH2:31][C@@H:32]2[CH2:34][O:33]2)=[C:6]([NH:8][C:9]([N:11]2[CH2:15][CH2:14][C@H:13]([OH:16])[CH2:12]2)=[O:10])[CH:7]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 146490Benzenesulfonic acid, 3-nitro-, (2S)-2-oxiranylmethyl esterHCID 68963403(3S)-N-(5-chloro-2-hydroxyphenyl)-3-hydroxypyrrolidine-1-carboxamide

Product 1

HCID 86601486(3S)-N-(5-chloro-2-[(2S)-oxiran-2-ylmethoxy]phenyl}-3-hydroxypyrrolidine-1-carboxamideYield 29.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (3S)-N-(5-chloro-2-hydroxyphenyl)-3-hydroxypyrrolidine-1-carboxamide (232 mg, 0.90 mmol), (2S)-oxiran-2-ylmethyl 3-nitrobenzenesulfonate (234 mg, 0.90 mmol) and caesium carbonate (369 mg, 1.13 mmol) in dimethylformamide (9 mL) was stirred at room temperature, over night. The mixture was partitioned between water and ethyl acetate, and the organic phase was washed twice with water and once with brine, and finally concentrated. The crude material was purified by HPLC on C 18 (“Kromasil” column, 10 um, acetonitrile/water 35/65 to 85/15 over 30 min), yielding the titled compound (82 mg, 29%).

Workup

  1. customThe mixture was partitioned between water and ethyl acetate
  2. washthe organic phase was washed twice with water and once with brine
  3. concentrationfinally concentrated
  4. customThe crude material was purified by HPLC on C 18 (“Kromasil” column, 10 um, acetonitrile/water 35/65 to 85/15 over 30 min)

Sources & evidence

ORD record
ord-77b28f2f2a0f482b9fa9b0e4282eccd5
Source dataset
uspto-grants-2008_11
Patent number
US07449475B2

Reaction notes

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