Potassium Carbonate → Tert-butyl 4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(5-fluorobiphenyl-2-yl)piperidine-1-carboxylate

HRID 391374

반응식

HRID 391374 반응식
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1([CH2:22][O:23][CH2:24][C:25]2[CH:26]=[C:27]([C:35]3[CH:40]=[CH:39][C:38]([C:41]#[N:42])=[CH:37][CH:36]=3)[CH:28]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:30]=2)[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1.[C:43]1(B(O)O)[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:41]([C:38]1[CH:37]=[CH:36][C:35]([C:27]2[CH:28]=[C:29]([C:31]([F:32])([F:33])[F:34])[CH:30]=[C:25]([CH2:24][O:23][CH2:22][C:9]3([C:3]4[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=4[C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH2:14]3)[CH:26]=2)=[CH:40][CH:39]=1)#[N:42]

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 58993540Tert-butyl 4-(2-bromo-4-fluorophenyl)-4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)piperidine-1-carboxylate

생성물 1

HCID 58993654Tert-butyl 4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(5-fluorobiphenyl-2-yl)piperidine-1-carboxylate수율 40.3%

시약·촉매·용매 1

HCID 178418397HCID 178418397, 화합물촉매

반응 조건

온도
120 °C

실험 절차

A mixture of tert-butyl 4-(2-bromo-4-fluorophenyl)-4-(((4′-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)piperidine-1-carboxylate (100 mg, 0.15 mmol), phenyl boronic acid (19 mg, 0.15 mmol), potassium carbonate (43 mg, 0.31 mmol) and tetrakis(triphenylphosphine)palladium(0) (18 mg, 0.15 mmol) were placed in a sealable vessel and degassed with nitrogen for 5 min. The vessel was then sealed and heated at 120° C. for 3 h. The reaction was poured into brine (20 mL) and extracted with ethyl acetate (4×5 mL). The combined organic layers were dried (MgSO4) and evaporated to dryness. The resulting residue was purified by chromatography on SiO2 with a ethyl acetate/hexanes gradient from 12% to 100%. The product tert-butyl 4-(((4′-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(5-fluorobiphenyl-2-yl)piperidine-1-carboxylate (39 mg, 39%) was isolated as a clear oil. 1H-NMR (CDCl3, 400 MHz) δ 7.68-7.76 (m, 3H), 7.55 (d, J=8.4 Hz, 2H), 7.44 (m, 3H), 7.18-7.28 (m, 3H), 7.03 (m, 1H), 6.94 m, 2H), 6.67 (m, 1H), 4.52 (s, 2H), 3.52 (m, 2H), 3.47 (s, 2H), 2.90 (m, 2H), 1.91 (m, 2H), 1.45 (m, 2H), 1.38 (s, 9H). Mass spec.: 645.2 (M+H).

후처리

  1. customwere placed in a sealable vessel
  2. customdegassed with nitrogen for 5 min
  3. customThe vessel was then sealed
  4. additionThe reaction was poured into brine (20 mL)
  5. extractionextracted with ethyl acetate (4×5 mL)
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. customevaporated to dryness
  8. customThe resulting residue was purified by chromatography on SiO2 with a ethyl acetate/hexanes gradient from 12% to 100%

출처 및 근거

ORD 기록
ord-1c8af16cc8e54f14ba9e06b48015f4dc
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08383821B2

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