Sodium Hydroxide → (S)-[6-(3-Fluoro-4-methylphenyl)-3,3-dimethyl-2-oxopiperidin-1-yl]acetic acid

HRID 1866646Notes

Reaction equation

HRID 1866646 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[NH:14][C:13](=[O:15])[C:12]([CH3:17])([CH3:16])[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[CH3:8].[H-].[Na+].Br[CH2:21][C:22]([O:24]C)=[O:23].[OH-].[Na+]>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[N:14]([CH2:21][C:22]([OH:24])=[O:23])[C:13](=[O:15])[C:12]([CH3:17])([CH3:16])[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[CH3:8]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 66973541(S)-6-(3-Fluoro-4-methylphenyl)-3,3-dimethylpiperidin-2-one

Product 1

HCID 57974106(S)-[6-(3-Fluoro-4-methylphenyl)-3,3-dimethyl-2-oxopiperidin-1-yl]acetic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (S)-6-(3-fluoro-4-methylphenyl)-3,3-dimethylpiperidin-2-one from Step A (80 mg, 0.340 mmol) in DMF (3 mL) at ambient temperature was added NaH (19 mg of a 60% dispersion in oil, 0.476 mmol). After 15 min, methyl bromoacetate (0.051 mL, 0.544 mmol) was added and the mixture was stirred for 16 h. Sodium hydroxide (0.061 mL of a 10 M solution, 0.612 mmol) was added and the mixture stirred for 2 h. The crude product was purified directly by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. The compound was further purified by SFC, utilizing a ChiralPak AD column and eluting with CO2:MeOH—91:9, to give the title compound. MS: m/z=294 (M+1).

Workup

  1. stirringthe mixture stirred for 2 h
  2. customThe crude product was purified directly by HPLC
  3. washeluting with a gradient of H2O
  4. customThe compound was further purified by SFC
  5. washeluting with CO2

Sources & evidence

ORD record
ord-678985bcd4c14df5897e4702df78a5e1
Source dataset
uspto-grants-2009_12
Patent number
US07629338B2

Reaction notes

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