Ethanol → (4-Fluorophenyl)(1-[2-methyl-7,8-dihydro-1,6,9-trioxa-3-aza-cyclopenta[a]naphthalen-8-ylmethyl]-4-piperidinyl)methanone

HRID 2414845ノート

反応式

HRID 2414845 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]1[CH:41]=[CH:40][C:31]([C:32]([CH:34]2[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]2)=[O:33])=[CH:30][CH:29]=1.C(O)C.C(O)(=O)/C=C/C(O)=O>CS(C)=O>[F:27][C:28]1[CH:41]=[CH:40][C:31]([C:32]([CH:34]2[CH2:39][CH2:38][N:37]([CH2:12][CH:13]3[O:14][C:15]4[C:16](=[CH:17][CH:18]=[C:19]5[N:20]=[C:21]([CH3:24])[O:22][C:23]5=4)[O:25][CH2:26]3)[CH2:36][CH2:35]2)=[O:33])=[CH:30][CH:29]=1

参加物

6

反応物 4

HCID 702EthanolHCID 444972Fumaric AcidHCID 27244404-(4-Fluorobenzoyl)piperidineHCID 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 10158477(4-Fluorophenyl)(1-[2-methyl-7,8-dihydro-1,6,9-trioxa-3-aza-cyclopenta[a]naphthalen-8-ylmethyl]-4-piperidinyl)methanone収率 60.9%

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 (0.45 g, 1.2 mmole) and 4-(4-fluorobenzoyl)piperidine (0.73 g, 3.54 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 cooled to room temperature and 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 0.28 g of the (S)-enantiomer of the title compound. This was recrystallized from ethanol with the addition of one equivalent of fumaric acid to give 0.30 g of pale yellow solid, m.p. 229-230° C.

後処理

  1. temperatureAfter completion, the reaction was cooled to room temperature
  2. custompartitioned 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 0.28 g of the (S)-enantiomer of the title compound

出典と根拠

ORDレコード
ord-ada2d3e6b067451ebb097a8d9e7599e5
出典データセット
uspto-grants-2004_11
特許番号
US06815448B2

反応ノート

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