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Water → (S,R) 1-Morpholin-2-yl-1-phenyl-2-(2-trifluoromethoxy-phenyl)-ethanol hydrochloride

HRID 899086
ノート
印刷プレビュー

反応式

HRID 899086 の反応式
[ClH:1].C([N:9]1[CH2:14][CH2:13][O:12][CH:11]([C:15]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)([OH:28])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[O:23][C:24]([F:27])([F:26])[F:25])[CH2:10]1)C1C=CC=CC=1.O>[Pd].CC(O)C>[ClH:1].[NH:9]1[CH2:14][CH2:13][O:12][C@@H:11]([C@:15]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)([OH:28])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[O:23][C:24]([F:27])([F:26])[F:25])[CH2:10]1
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 2

HCID 962WaterHCID 692922921-(4-Benzyl-morpholin-2-yl)-1-phenyl-2-(2-trifluoromethoxy-phenyl)-ethanol hydrochloride

生成物 1

HCID 69292906(S,R) 1-Morpholin-2-yl-1-phenyl-2-(2-trifluoromethoxy-phenyl)-ethanol hydrochloride収率 81%

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 3776Isopropanol溶媒

実験手順

Alternatively, the following method may be used. In a glass-lined nitrogen purged hydrogenator are charged 1-(4-Benzyl-morpholin-2-yl)-1-phenyl-2-(2-trifluoromethoxy-phenyl)-ethanol hydrochloride (150 g, 303.7 mmol), demineralized water (352 mL), i-PrOH (375 mL) and 5% Pd/C (30 g, 50% water, Johnson & Matthey type 440). The heterogeneous reaction mixture was then purged 5 times with 25 psi nitrogen then purged 5 times with 50 psi hydrogen, and the hydrogenation was performed at RT. The initial Tmass was 22° C. and the maximum Tmass during the hydrogenation was 23° C. The reactor was stirred vigorously. In-process analysis after 2 hours indicated complete hydrogenolysis. The hydrogenation was stopped after 3 hours. The nitrogen purged reaction mixture was then filtered at RT through an hyflo filter (56 g), impregnated beforehand with 75 mL of a 50/50 v/v isopropanol/water mixture and washed with 300 mL of a 50/50 v/v isopropanol/water mixture. The filtrates were stored overnight at RT. The filtrates were concentrated at 40-50° C. under reduced pressure (typical 622 g distilled). The reaction mixture was cooled to RT and post-agitated. After 3 hours, 1 mL of the solution was taken and cooled to 0° C. to initiate crystallization. These seeds were added to the reaction mixture and precipitation was observed within a few minutes. The mixture was post-agitated at RT for 2 hours. The crystals were filtered and rinsed with H20 (30 mL). Then, the precipitate was dried under reduced pressure (400 mmHg) with a nitrogen flow (0.1 bar) for 4 hours affording the title compound as the hydrate polymorph (103.5 g, 81% yield).

後処理

  1. customThe heterogeneous reaction mixture was then purged 5 times with 25 psi nitrogen
  2. customthen purged 5 times with 50 psi hydrogen
  3. customwas performed at RT
  4. customwas 22° C.
  5. customwas 23° C
  6. waitThe hydrogenation was stopped after 3 hours
  7. customThe nitrogen purged
  8. customreaction mixture
  9. filtrationwas then filtered at RT through an hyflo
  10. filtrationfilter (56 g)
  11. washwashed with 300 mL of a 50/50 v/v isopropanol/water mixture
  12. waitThe filtrates were stored overnight at RT
  13. concentrationThe filtrates were concentrated at 40-50° C. under reduced pressure (typical 622 g distilled)
  14. stirringpost-agitated
  15. waitAfter 3 hours
  16. temperaturecooled to 0° C.
  17. customcrystallization
  18. additionThese seeds were added to the reaction mixture and precipitation
  19. waitwas observed within a few minutes
  20. stirringThe mixture was post-agitated at RT for 2 hours
  21. filtrationThe crystals were filtered
  22. washrinsed with H20 (30 mL)
  23. customThen, the precipitate was dried under reduced pressure (400 mmHg) with a nitrogen flow (0.1 bar) for 4 hours

出典と根拠

ORDレコード
ord-4d5aff93cb334157a65bf861409b0bc5
出典データセット
uspto-grants-2008_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07354920B2

反応ノート

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