Potassium Carbonate → 2-{3-[(2,2-Difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl}ethanol

HRID 2184192ノート

反応式

HRID 2184192 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=O)[C:10]([F:18])([F:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[C:4]([F:20])[C:3]=1[CH2:21][CH2:22][OH:23].C([O-])([O-])=O.[K+].[K+]>C1COCC1.O>[F:18][C:10]([F:17])([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[CH2:9][NH:8][C:5]1[C:4]([F:20])=[C:3]([CH2:21][CH2:22][OH:23])[C:2]([Cl:1])=[CH:7][CH:6]=1

参加物

5

反応物 2

HCID 11430Potassium CarbonateHCID 22475352N-[4-chloro-2-fluor-3-(2-hydroxyethyl)phenyl]-2,2-difluoro-2-phenylacetamide

生成物 1

HCID 224753362-{3-[(2,2-Difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl}ethanol収率 81%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution N-[4-chloro-2-fluor-3-(2-hydroxyethyl)phenyl]-2,2-difluoro-2-phenylacetamide (1.05 g, 3.06 mmol), as prepared according to the procedure in the preceding step, in THF (12 mL) at 0° C. under argon was added a solution of borane-THF complex in THF (12.3 mL, 12.3 mmol, 1.0 M) over a period of 10 minutes, and the reaction mixture continued to stir until the ice-bath expired. The reaction mixture was heated at reflux for 20 hours, and allowed to cool to room temperature. A solution of K2CO3 (1.7 g, 12 mmol) in H2O (12 mL) was added, the THF was removed in vacuo, and the mixture was extracted with DCM (3 times). The extracts were combined, washed with brine, dried over Na2SO4, concentrated, and flash chromatographed on silica gel eluting with EtOAC/DCM (0 and 2.5%) to give the title compound (815 mg, 81% yield) as a colorless oil. 1H-NMR (400 MHz, CDCl3) δ 7.52-7.43 (m, 5H), 6.97 (dd, J=8.8, 1.7 Hz, 1H), 6.51 (t, J=8.9 Hz, 1H), 4.17 (bs, 1H), 3.83 (t, J=6.9 Hz, 2H), 3.74 (dt, J=13.4, 6.6 Hz, 2H), 3.04 (dt, J=6.9, 2.4 Hz, 2H), 1.43 (s, 1H). Mass spectrum (LCMS, ESI) calc'd for C16H16ClF3NO (M+H): 330.1. Found: 330.3.

後処理

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 20 hours
  3. customthe THF was removed in vacuo
  4. extractionthe mixture was extracted with DCM (3 times)
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customflash chromatographed on silica gel eluting with EtOAC/DCM (0 and 2.5%)

出典と根拠

ORDレコード
ord-7b58971db7654f9a8571a635cb556877
出典データセット
uspto-grants-2005_05
特許番号
US06900231B2

反応ノート

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