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Potassium Hydroxide → tert-Butyl 4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

HRID 391419
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인쇄 미리보기

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HRID 391419 반응식
Br[C:2]1[CH:3]=[C:4]([CH:28]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:30]=1)[CH2:5][O:6][CH2:7][C:8]1([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.[C:35]([C:37]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1)#[N:36].[OH-].[K+]>O1CCCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:35]([C:37]1[CH:42]=[CH:41][C:40]([C:2]2[CH:30]=[C:29]([C:31]([F:33])([F:34])[F:32])[CH:28]=[C:4]([CH2:5][O:6][CH2:7][C:8]3([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:12][CH2:13]3)[CH:3]=2)=[CH:39][CH:38]=1)#[N:36]
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참가 물질

6

반응물 3

HCID 14797Potassium HydroxideHCID 27343264-Cyanophenylboronic acidHCID 58993524tert-Butyl 4-((3-bromo-5-(trifluoromethyl)benzyloxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

생성물 1

HCID 58993637tert-Butyl 4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

시약·촉매·용매 2

HCID 11979704
Tetrakis(triphenylphosphine)palladium
촉매
HCID 8028Tetrahydrofuran용매

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온도
120 °C

실험 절차

tert-Butyl 4-((3-bromo-5-(trifluoromethyl)benzyloxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (130.0 mg, 0.24 mmol), 4-cyanophenylboronic acid (140.0 mg, 0.95 mmol), and tetrakis(triphenylphosphine) palladium(0) (37.1 mg, 0.024 mmol) were combined in dry tetrahydrofuran (3 mL) in a microwave tube and sealed. The mixture was flushed with nitrogen. To this was added potassium hydroxide (1 N in water, 0.75 mL, 0.75 mmol). The mixture was heated at 120° C. for 1 h via microwave. After cooling to room temperature, the reaction mixture was concentrated and purified by flash chromatography on silica gel (25% ethyl acetate/hexanes) to afford 61.0 mg (48%). 1H-NMR (CDCl3, 500 MHz) δ 7.74-7.76 (m, 2H), 7.67 (s, 1H), 7.57-7.60 (m, 2H), 7.41 (s, 1H), 7.40 (s, 1H), 7.29-7.32 (m, 2H), 6.98-7.02 (m, 2H), 4.47 (s, 2H), 3.71-3.74 (m, 2H), 3.43 (s, 2H), 3.01-3.06 (m, 2H), 2.14-2.17 (m, 2H), 1.82-1.88 (m, 2H), 1.42 (s, 9H). Mass spec.: 569.25 (MH)+.

후처리

  1. customsealed
  2. customThe mixture was flushed with nitrogen
  3. temperatureAfter cooling to room temperature
  4. concentrationthe reaction mixture was concentrated
  5. custompurified by flash chromatography on silica gel (25% ethyl acetate/hexanes)
  6. customto afford 61.0 mg (48%)

출처 및 근거

ORD 기록
ord-42de0d83e2c5445c9c8214e2d315bdec
출처 데이터셋
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08383821B2

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