Triethylamine → 4,4-Difluorocyclohexanecarboxylic acid

HRID 2422385Notes

Reaction equation

HRID 2422385 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(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=[O:31])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:31])[CH2:15][CH2:16]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 98792204,4-Difluoro-N-(3-oxo-1-phenylpropyl)cyclohexane-1-carboximidic acid

Product 1

HCID 27791364,4-Difluorocyclohexanecarboxylic acid

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 40 mg (0.1 mmol) of 3-(4-methanesulfonylbenzyl)-bicyclo[3.2.1]-1α,3,8-triaza-spiro[4.5]dodecan-2,4-dione hydrochloride in 1.7 mL of anhydrous DCE were added successively 24 mg (0.1 mmol) of 4,4-difluoro-cyclohexanecarboxylic acid ((S)-3-oxo-1-phenyl-propyl)-amide and 17 μL (0.12 mmol) of triethylamine. The reaction mixture was agitated at room temperature for 10 minutes before adding 26 mg (0.125 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 Bond Elut (ethyl acetate to 5% methanol/DCM) to yield the 4,4-difluoro-cyclohexanecarboxylic acid {(S)-3-[3-(4-methanesulfonylbenzyl)-bicyclo[3.2.1]-2,4-dioxo-1α,3,8-triaza-spiro[4.5]dodec-8-yl]-1-phenyl-propyl}-amide as a white solid (40 mg, 62.3%).

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 Bond Elut (ethyl acetate to 5% methanol/DCM)

Sources & evidence

ORD record
ord-a2be8213b7234d1ba5b76e55baaa8ecc
Source dataset
uspto-grants-2011_06
Patent number
US07960403B2

Reaction notes

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