Sodium Hydroxide → (2S,4R)-2-(3-Bromo-4-carboxy-phenylcarbamoyl)-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1527360Notes

Reaction equation

HRID 1527360 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]=[CH:20][C:19]([C:22]([O:24]C)=[O:23])=[C:18]([Br:26])[CH:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>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]=[CH:20][C:19]([C:22]([OH:24])=[O:23])=[C:18]([Br:26])[CH:17]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 68284187(2S,4R)-2-(3-Bromo-4-methoxycarbonyl-phenylcarbamoyl)-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68284410(2S,4R)-2-(3-Bromo-4-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-4-methoxycarbonyl-phenylcarbamoyl)-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester (400 mg, 0.898 mmol) in MeOH (9 mL) was added a 2N aqueous NaOH solution (1.78 mL, 3.59 mmol). The reaction mixture was stirred at RT for 20 h and then evaporated under reduced pressure. The residue was taken up in water and the aqueous phase was acidified (pH 2 to 3) by adding 0.1N aqueous HCl. The resulting suspension was extracted with EtOAc (4×) and the combined organics were concentrated under reduced pressure to afford the crude title compound as a pale yellow solid. This product was used in the next reaction step without further purification. MS (LC/MS): 454 [M+Na]+, 374 [MH−tBu]+, 330 [MH−Boc]+; tR (HPLC conditions b): 3.41 min.

Workup

  1. customevaporated under reduced pressure
  2. additionby adding 0.1N aqueous HCl
  3. extractionThe resulting suspension was extracted with EtOAc (4×)
  4. concentrationthe combined organics were concentrated under reduced pressure

Sources & evidence

ORD record
ord-132fac9d3a1945638a41031efe1e1d2b
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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