Sodium Hydroxide → 1-(tert-Butoxycarbonyl)-5,5-difluoropiperidine-3-carboxylic acid

HRID 931254Notes

Reaction equation

HRID 931254 reaction equation
[F:1][C:2]1([F:19])[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:5][CH:4]([C:15]([O:17]C)=[O:16])[CH2:3]1.[OH-].[Na+]>CO>[C:11]([O:10][C:8]([N:6]1[CH2:7][C:2]([F:1])([F:19])[CH2:3][CH:4]([C:15]([OH:17])=[O:16])[CH2:5]1)=[O:9])([CH3:14])([CH3:12])[CH3:13]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 683092621-Tert-butyl 3-Methyl 5,5-difluoropiperidine-1,3-dicarboxylate

Product 1

HCID 665217431-(tert-Butoxycarbonyl)-5,5-difluoropiperidine-3-carboxylic acidYield 87.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 1-tert-butyl 3-methyl 5,5-difluoropiperidine-1,3-dicarboxylate (3.0 g, 10.74 mmol) in methanol (35 mL) was added a 1N aqueous solution of sodium hydroxide (20 mL) at below 5° C. The mixture was warmed to room temperature, and after 16 h, the mixture was concentrated under reduced pressure. The remaining aqueous layer was acidified with a 1N aqueous solution of hydrochloric acid (to pH˜4) and was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford 1-(tert-butoxycarbonyl)-5,5-difluoropiperidine-3-carboxylic acid (2.5 g) as a pale yellow solid which was used without further purification.

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. extractionwas extracted with ethyl acetate
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7366f3a97222432c9b00406c4f128ca0
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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