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

HRID 511071노트

반응식

HRID 511071 반응식
[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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 9811564Bis(dibenzylideneacetone)palladium촉매

반응 조건

온도
65 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-a623f685b8a24c1da5683b907081a0dd
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096524B2

반응 노트

불러오는 중…