Triethylamine → 4,4-Difluorocyclohexanecarboxylic acid

HRID 1644245Notes

Reaction equation

HRID 1644245 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(N(CC)CC)C>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 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 98792204,4-Difluoro-N-(3-oxo-1-phenylpropyl)cyclohexane-1-carboximidic acid

Product 1

HCID 27791364,4-Difluorocyclohexanecarboxylic acidYield 148.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To 21.1 mg (0.072 mmol) of 1-methyl-3-(tetrahydropyran-4-ylmethyl)-bicyclo[3.2.1]-1β,3,8-triaza-spiro[4.5]dodecan-2-one in 1.5 mL of DCE was added 21.2 mg (0.072 mmol, 1 eq.) of 4,4-difluoro-cyclohexanecarboxylic acid ((S)-3-oxo-1-phenyl-propyl)-amide, 19 mg (0.09 mmol, 1.25 eq.) of sodium triacetoxyborohydride and 12 μL (0.086 mmol, 1.2 eq.) of triethylamine. The reaction mixture was stirred overnight at room temperature and concentrated in vacuo. The crude was purified by flash chromatography on silica gel (DCM/MeOH: 0 to 100) and redissolved in 1 mL of methanol and 100 μL of HCl (1N). The solution was then concentrated in vacuo and diluted with 2 mL of water to give after lyophilization 17.5 mg (40%) of 4,4-difluoro-cyclohexanecarboxylic acid {(S)-3-[1-methyl-3-(tetrahydropyran-4-ylmethyl)-bicyclo[3.2.1]-2-oxo-1β,3,8-triaza-spiro[4.5]dodec-8-yl]-1-phenyl-propyl}-amide hydrochloride.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe crude was purified by flash chromatography on silica gel (DCM/MeOH: 0 to 100)
  3. dissolutionredissolved in 1 mL of methanol
  4. concentrationThe solution was then concentrated in vacuo
  5. additiondiluted with 2 mL of water

Sources & evidence

ORD record
ord-0fa43a03e25345d1aaf532ea064bf06f
Source dataset
uspto-grants-2012_02
Patent number
US08124613B2

Reaction notes

Loading…