Sodium Thiosulfate → (2R,5R)-2-(tert-butyldimethylsilyloxy)-5-(2,3-difluorophenyl)cycloheptanone

HRID 1666126ノート

反応式

HRID 1666126 の反応式
[Si:1]([O:8][CH:9]1[CH2:15][CH2:14][CH:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:17]=2[F:23])[CH2:12][CH2:11][CH:10]1[OH:24])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[O-]S([O-])(=S)=O.[Na+].[Na+]>C(Cl)Cl.CCOCC>[Si:1]([O:8][C@@H:9]1[CH2:15][CH2:14][C@@H:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:17]=2[F:23])[CH2:12][CH2:11][C:10]1=[O:24])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

参加物

6

反応物 3

HCID 24477Sodium ThiosulfateHCID 159087TriacetoxyperiodinaneHCID 579114932-(Tert-butyldimethylsilyloxy)-5-(2,3-difluorophenyl)cycloheptanol

生成物 1

HCID 57911495(2R,5R)-2-(tert-butyldimethylsilyloxy)-5-(2,3-difluorophenyl)cycloheptanone

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 6344Dichloromethane溶媒

実験手順

In a 250 mL round-bottomed flask (t=g) was added 2-(tert-butyldimethylsilyloxy)-5-(2,3-difluorophenyl)cycloheptanol (1.73 g, 4.85 mmol) in CH2Cl2 (50 mL) to give a colorless solution. Dess-Martin Periodinane (2.264 g, 5.34 mmol) was added in one portion, and the mixture was stirred at room temperature overnight. 17 h: TLC showed complete conversion. It was diluted with Et2O and treated with 40 ml saturated Na2S2O3 and Na2HCO3 solution (1/1 mixture) until the milky solution became clear (10 min). The layers were separated and the aqueous layer was extracted with Et2O. The combined organic layers were washed with brine, dried with Na2SO4, and concentrated to a colorless oil (with some solids insoluble in hexane). Purification by FCC up to 40% Et2O in hexane afforded two peaks. They were individually pooled and concentrated. The less polar major one (978 mg, 55%) was a colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.02-6.90 (m, 3H), 4.34 (d, J=4.6 Hz, 1H), 2.82-2.75 (m, 2H), 2.54-2.46 (m, 1H), 2.45-2.32 (m, 1H), 2.17-1.98 (m, 2H), 1.90-1.68 (m, 3H), 0.94 (s, 9H), 0.08 (s, 6H); 13C NMR (125 MHz, CDCl3) δ 213.4, 150.7 (dd, J=247.6 and 13.4 Hz), 147.8 (dd, J=245.7 and 13.4 Hz), 137.5 (d, J=11.5 Hz), 127.7, 122.2, 114.7 (d, J=17.3 Hz), 79.0, 40.0, 39.2, 33.2, 30.7, 29.4, 25.8, 18.2, −5.0. The more polar minor one solidified upon standing to a white solid (698 mg, 39%). It was re-crystallized from hexane and X-ray analysis verified the anti-stereochemistry relation. 1H NMR (500 MHz, CDCl3) δ 7.10-6.97 (m, 2H), 6.97-6.90 (m, 1H), 4.34 (dd, J=3.0 and 9.7 Hz, 1H), 3.04-2.94 (m, 1H), 2.80-2.70 (m, 1H), 2.62-2.50 (m, 1H), 2.18-1.72 (m, 6H), 0.90 (s, 9H), 0.10 (s, 3H), 0.06 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 211.0, 150.8 (dd, J=248.6 and 13.5 Hz), 148.1 (dd, J=246.7 and 12.5 Hz), 136.4 (d, J=11.5 Hz), 124.2, 122.3, 115.1 (d, J=17.3 Hz), 78.4, 40.3, 39.4, 34.3, 33.0, 30.4, 25.9, 18.5, −4.5, −5.1.

後処理

  1. customto give a colorless solution
  2. custom17 h
  3. custom(10 min)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with Et2O
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried with Na2SO4
  8. concentrationconcentrated to a colorless oil (with some solids insoluble in hexane)
  9. customPurification by FCC up to 40% Et2O in hexane
  10. customafforded two peaks
  11. concentrationconcentrated
  12. customIt was re-crystallized from hexane and X-ray analysis

出典と根拠

ORDレコード
ord-721a4df0d6714b11a916036890af23a4
出典データセット
uspto-grants-2011_10
特許番号
US08044043B2

反応ノート

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