4-[3-(Trifluoromethyl)phenyl]-4-piperidinol → 1-(2-Methyl-7,8-dihydro-1,6,9-trioxa-3-aza-cyclopenta[a]naphthalen-8-ylmethyl)-4-[3-(trifluoromethyl)phenyl]-4-piperidinol

HRID 2414844

反応式

HRID 2414844 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.[F:27][C:28]([F:43])([F:42])[C:29]1[CH:30]=[C:31]([C:35]2([OH:41])[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[CH:32]=[CH:33][CH:34]=1>CS(C)=O>[CH3:24][C:21]1[O:22][C:23]2=[C:15]3[C:16](=[CH:17][CH:18]=[C:19]2[N:20]=1)[O:25][CH2:26][CH:13]([CH2:12][N:38]1[CH2:37][CH2:36][C:35]([C:31]2[CH:32]=[CH:33][CH:34]=[C:29]([C:28]([F:27])([F:42])[F:43])[CH:30]=2)([OH:41])[CH2:40][CH2:39]1)[O:14]3

参加物

4

反応物 2

HCID 752554-[3-(Trifluoromethyl)phenyl]-4-piperidinolHCID 11245807(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-ylmethyl 4-methylbenzenesulfonate

生成物 1

HCID 102755481-(2-Methyl-7,8-dihydro-1,6,9-trioxa-3-aza-cyclopenta[a]naphthalen-8-ylmethyl)-4-[3-(trifluoromethyl)phenyl]-4-piperidinol

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
80 °C

実験手順

(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-ylmethyl 4-methylbenzenesulfonate (0.43 g, 1.14 mmole) and 4-[3-(trifluoromethyl)phenyl]-4-piperidinol (0.84 g, 3.43 mmole) were combined in 10 mL of DMSO under nitrogen. This solution was heated to 80° C. under nitrogen for 4 hours. After completion, the reaction was allowed to cool to room temperature and was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic phase was washed with brine, dried over magnesium sulfate and concentrated in vacuum. The resulting crude oil was column chromatographed on silica gel using first methylene chloride to remove impurities and then 1% methanol/methylene chloride to elute 0.33 g of the (S)-enantiomer of the title compound, m.p. 148-151° C.

後処理

  1. temperatureto cool to room temperature
  2. customwas partitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  3. washThe organic phase was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuum
  6. customchromatographed on silica gel using first methylene chloride
  7. customto remove impurities
  8. wash1% methanol/methylene chloride to elute 0.33 g of the (S)-enantiomer of the title compound, m.p. 148-151° C.

出典と根拠

ORDレコード
ord-61d8c17849ec41a780ae47ef11fbf038
出典データセット
uspto-grants-2004_11
特許番号
US06815448B2

関連ノート

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