2-Morpholinoethanol → {1-[4-Cyano-3-fluoro-5-(2-morpholin-4-yl-ethoxy)-phenyl]-piperidin-4-yl}-carbamic acid tert-butyl ester

HRID 2054894

反応式

HRID 2054894 の反応式
[C:1]([O:5][C:6](=[O:24])[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[C:18](F)[C:17]([C:21]#[N:22])=[C:16]([F:23])[CH:15]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[OH:25][CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[C:1]([O:5][C:6](=[O:24])[NH:7][CH:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:19]=[C:18]([O:25][CH2:26][CH2:27][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:17]([C:21]#[N:22])=[C:16]([F:23])[CH:15]=2)[CH2:12][CH2:13]1)([CH3:2])([CH3:4])[CH3:3]

参加物

5

反応物 3

HCID 611632-MorpholinoethanolHCID 2724254Sodium bis(trimethylsilyl)amideHCID 21090459[1-(4-Cyano-3,5-difluoro-phenyl)-piperidin-4-yl]-carbamic acid tert-butyl ester

生成物 1

HCID 59656697{1-[4-Cyano-3-fluoro-5-(2-morpholin-4-yl-ethoxy)-phenyl]-piperidin-4-yl}-carbamic acid tert-butyl ester収率 61%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of 0.10 g (0.30 mmol) of [1-(4-cyano-3,5-difluoro-phenyl)-piperidin-4-yl]-carbamic acid tert-butyl ester and 0.040 mL (0.33 mmol) of 4-(2-hydroxyethyl)-morpholine in THF (15 mL), cooled to 0° C., was added 0.60 mL (0.60 mmol) of sodium bis(trimethylsilyl)amide as a 1.0 M solution in THF. The reaction was stirred at 0° C. for 30 min then warmed to 60° C. for 6 h. The reaction was cooled to room temperature and excess base was consumed by the addition of a saturated aqueous solution of NH4Cl. The mixture was diluted with H2O and washed with EtOAc. The combined organic phase was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude residue was purified by flash silica gel chromatography to provide 0.081 g (61%) of {1-[4-cyano-3-fluoro-5-(2-morpholin-4-yl-ethoxy)-phenyl]-piperidin-4-yl}-carbamic acid tert-butyl ester as a white foam.

後処理

  1. temperaturethen warmed to 60° C. for 6 h
  2. temperatureThe reaction was cooled to room temperature
  3. customexcess base was consumed by the addition of a saturated aqueous solution of NH4Cl
  4. additionThe mixture was diluted with H2O
  5. washwashed with EtOAc
  6. washThe combined organic phase was washed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customThe crude residue was purified by flash silica gel chromatography

出典と根拠

ORDレコード
ord-0d54c701f14443d08aaf7a22baf65017
出典データセット
uspto-grants-2008_02
特許番号
US07329764B2

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