Hydrochloric Acid → 1-[4-(Trifluoromethyl)phenyl]piperidin-4-ol

HRID 511071ノート

反応式

HRID 511071 の反応式
[OH:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.Br[C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=1.C1(P(C2CCCCC2)C2(C)CC=CC=C2C2C=CC=CC=2)CCCCC1.O1CCCC1.Cl.C(=O)([O-])O.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:16][C:15]([F:18])([F:17])[C:12]1[CH:13]=[CH:14][C:9]([N:5]2[CH2:6][CH2:7][CH:2]([OH:1])[CH2:3][CH2:4]2)=[CH:10][CH:11]=1

参加物

8

反応物 6

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 79341Piperidin-4-olHCID 516892Sodium BicarbonateHCID 66672255Dicyclohexyl-(1-methyl-2-phenylcyclohexa-2,4-dien-1-yl)phosphane

生成物 1

HCID 220976741-[4-(Trifluoromethyl)phenyl]piperidin-4-ol

試薬・触媒・溶媒 1

HCID 9811564Bis(dibenzylideneacetone)palladium触媒

反応条件

温度
65 °C

実験手順

A mixture of 4-hydroxypiperidine (100 mg; 0.99 mmol), 4-bromo benzotrifluoride (0.167 mL, 1.19 mmol), tris(dibenzylideneacetone)dipalladium (37 mg; 0.04 mmol) and 2-(dicyclohexylphosphino)-2-methylbiphenyl (29 mg; 0.08 mmol) is thoroughly flushed with argon and tetrahydrofuran is added (1 mL). A molar solution of bis-(trimethylsilyl)-lithium amide in tetrahydrofuran (1.9 mL, 1.90 mmol) is added and the reaction mixture is heated at 65° C. After 17 hours reaction time, aq. 1M hydrochloric acid (7.5 mL) is added and the mixture is stirred for 15 minutes before neutralization by addition of aq. sat. sodium hydrogencarbonate. The mixture is extracted with ethyl acetate (2×10 mL). The combined organic layers are dried over sodium sulfate, filtered and evaporated under reduced pressure to yield crude 1-(4-trifluoromethyl-phenyl)-piperidin-4-ol.

後処理

  1. customis thoroughly flushed with argon and tetrahydrofuran
  2. additionis added (1 mL)
  3. additionis added
  4. extractionThe mixture is extracted with ethyl acetate (2×10 mL)
  5. dry with materialThe combined organic layers are dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated under reduced pressure

出典と根拠

ORDレコード
ord-a623f685b8a24c1da5683b907081a0dd
出典データセット
uspto-grants-2015_08
特許番号
US09096524B2

反応ノート

読み込み中…