Lithium hydroxide, monohydrate → (2S,4R)-2-(3-Bromo-5-carboxy-phenylcarbamoyl)-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1527358Notes

Reaction equation

HRID 1527358 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([F:13])[CH2:10][C@H:9]1[C:14](=[O:27])[NH:15][C:16]1[CH:21]=[C:20]([C:22]([O:24]C)=[O:23])[CH:19]=[C:18]([Br:26])[CH:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[Li].O>CO>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([F:13])[CH2:10][C@H:9]1[C:14](=[O:27])[NH:15][C:16]1[CH:21]=[C:20]([C:22]([OH:24])=[O:23])[CH:19]=[C:18]([Br:26])[CH:17]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 68284215(2S,4R)-2-(3-Bromo-5-methoxycarbonyl-phenylcarbamoyl)-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68284160(2S,4R)-2-(3-Bromo-5-carboxy-phenylcarbamoyl)-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (2S,4R)-2-(3-bromo-5-methoxycarbonyl-phenylcarbamoyl)-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester (480 mg, 1.08 mmol) in MeOH (10 mL), cooled to 0° C. was added LiOH.H2O (271 mg, 6.47 mmol) and the resulting solution was allowed to reach RT and stirred for 5 h. MeOH was concentrated and the residue was diluted in CH2Cl2, HCl 1 M was added (pH=1) and the layers were separated. The aqueous layer was back extracted twice with CH2Cl2 and the combined organic layers were dried over Na2SO4, filtered and concentrated to give the desired material which was used without further purification in the next step. MS (LC-MS): 453.0/455.0 [M+Na]+, 375.1/377.1 [MH−tBu]+, 331.1/333.1 [MH−Boc]+, 429.0/431.0 [M−H]−; tR (HPLC conditions a): 3.27 min.

Workup

  1. customto reach RT
  2. concentrationMeOH was concentrated
  3. additionthe residue was diluted in CH2Cl2
  4. additionHCl 1 M was added (pH=1)
  5. customthe layers were separated
  6. extractionThe aqueous layer was back extracted twice with CH2Cl2
  7. dry with materialthe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-ab2a560ec1834e12b7d6714ddc99a7e2
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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