Triethylamine → 4,4-Difluorocyclohexanecarboxylic acid

HRID 1644245ノート

反応式

HRID 1644245 の反応式
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

参加物

5

反応物 3

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

生成物 1

HCID 27791364,4-Difluorocyclohexanecarboxylic acid収率 148.1%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-0fa43a03e25345d1aaf532ea064bf06f
出典データセット
uspto-grants-2012_02
特許番号
US08124613B2

反応ノート

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