Sodium Bicarbonate → 4,4-Difluorocyclohexanecarboxylic acid

HRID 2422387Notes

Reaction equation

HRID 2422387 reaction equation
O=CC[C@H](N[C:12]([CH:14]1[CH2:19][CH2:18][C:17]([F:21])([F:20])[CH2:16][CH2:15]1)=[O:13])C1C=CC=CC=1.C(O[BH-](OC(=O)C)OC(=O)C)(=[O:24])C.[Na+].C(=O)(O)[O-].[Na+]>ClCCCl>[F:20][C:17]1([F:21])[CH2:18][CH2:19][CH:14]([C:12]([OH:13])=[O:24])[CH2:15][CH2:16]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 98792204,4-Difluoro-N-(3-oxo-1-phenylpropyl)cyclohexane-1-carboximidic acid

Product 1

HCID 27791364,4-Difluorocyclohexanecarboxylic acidYield 134.8%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To 19 mg (0.08 mmol) of 1,3-diethyl-bicyclo[3.2.1]-1β,3,8-triaza-spiro[4.5]dodecan-2-one and 23.6 mg (0.08 mmol) of 4,4-difluoro-cyclohexanecarboxylic acid ((S)-3-oxo-1-phenyl-propyl)-amide was added 1.5 mL of anhydrous DCE and 26.7 mg (0.12 mmol) of sodium triacetoxyborohydride. After an overnight agitation, 2 mL of saturated solution of sodium bicarbonate was added. The solution was then extracted with DCM (2×2 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude mixture was purified by semi-preparative HPLC (Method A) to yield 17.7 mg (40%) of 4,4-difluoro-cyclohexanecarboxylic acid {(S)-3-[1,3-diethyl-bicyclo[3.2.1]-2-oxo-1β,3,8-triaza-spiro[4.5]dodec-8-yl]-1-phenyl-propyl}-amide hydrochloride.

Workup

  1. extractionThe solution was then extracted with DCM (2×2 mL)
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude mixture was purified by semi-preparative HPLC (Method A)

Sources & evidence

ORD record
ord-fc8c2a75d259414ea2e09d5e384bd038
Source dataset
uspto-grants-2011_06
Patent number
US07960403B2

Reaction notes

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