(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-ylmethyl 4-methylbenzenesulfonate → 8-{[2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-yl]methyl}-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol

HRID 130395

反応式

HRID 130395 の反応式
CC1C=CC(S(O[CH2:12][C@H:13]2[CH2:26][O:25][C:16]3[CH:17]=[CH:18][C:19]4[N:20]=[C:21]([CH3:24])[O:22][C:23]=4[C:15]=3[O:14]2)(=O)=O)=CC=1.[C:27]1([C:33]2([OH:41])[CH2:39][CH:38]3[NH:40][CH:35]([CH2:36][CH2:37]3)[CH2:34]2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CS(C)=O.C(OCC)(=O)C>[CH3:24][C:21]1[O:22][C:23]2[C:15]3[O:14][CH:13]([CH2:12][N:40]4[CH:38]5[CH2:37][CH2:36][CH:35]4[CH2:34][C:33]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)([OH:41])[CH2:39]5)[CH2:26][O:25][C:16]=3[CH:17]=[CH:18][C:19]=2[N:20]=1

参加物

5

反応物 2

HCID 11245807(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-ylmethyl 4-methylbenzenesulfonateHCID 130912463-Phenyl-8-azabicyclo[3.2.1]octan-3-ol

生成物 1

HCID 102013708-{[2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-yl]methyl}-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
77.5 °C

実験手順

(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-ylmethyl 4-methylbenzenesulfonate (0.375 g, 1.00 mmole) and 3-phenyl-8-aza-bicyclo[3.2.1]-octan-3-ol (0.25 g, 1.2 mmole) were combined in 8 mL of DMSO. This solution was heated to 75-80° C. under nitrogen for 8 hours. After completion, the reaction was cooled to room temperature and diluted to 500 mL with ethyl acetate. The mixture was washed twice with 400 mL portions of saturated aqueous sodium bicarbonate, with 300 mL of water and twice with 400 mL of saturated brine, dried over sodium sulfate, filtered and concentrated in vacuum. The crude oil was column chromatographed on silica gel using first methylene chloride to remove impurities and then 0.5% methanol/methylene chloride to give, after concentration of the product fractions in vacuum, 0.12 g of the (S)-enantiomer of the title compound as an off-white solid, m.p. 203-205° C.

後処理

  1. temperatureAfter completion, the reaction was cooled to room temperature
  2. washThe mixture was washed twice with 400 mL portions of saturated aqueous sodium bicarbonate, with 300 mL of water and twice with 400 mL of saturated brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuum
  6. customchromatographed on silica gel using first methylene chloride
  7. customto remove impurities
  8. custom0.5% methanol/methylene chloride to give

出典と根拠

ORDレコード
ord-04405629bb87446194b52ecd67069589
出典データセット
uspto-grants-2008_06
特許番号
US07381723B2

関連ノート

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