Triethylamine → 4,4-Difluorocyclohexanecarboxylic acid

HRID 1644245노트

반응식

HRID 1644245 반응식
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

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 98792204,4-Difluoro-N-[(1S)-3-oxo-1-phenylpropyl]cyclohexanecarboxamide

생성물 1

HCID 27791364,4-Difluorocyclohexanecarboxylic acid수율 148.1%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0fa43a03e25345d1aaf532ea064bf06f
출처 데이터셋
uspto-grants-2012_02
특허 번호
US08124613B2

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