Sodium t-butoxide → 1-[2-Fluoro-4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]-4-{[1-(1-methylethyl)-4-piperidinyl]methyl}piperidine

HRID 1869640

반응식

HRID 1869640 반응식
CC(C)([O-])C.[Na+].[CH3:7][CH:8]([N:10]1[CH2:15][CH2:14][CH:13]([CH2:16][CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[CH2:12][CH2:11]1)[CH3:9].Br[C:24]1[CH:29]=[CH:28][C:27]([C:30]2[O:34][N:33]=[C:32]([CH3:35])[N:31]=2)=[CH:26][C:25]=1[F:36]>C1(C)C=CC=CC=1.CC(O)=O.CC(P(C(C)(C)C)C1C(C2[C-]=CC=CC=2)=CC=CC=1)(C)C.[Pd]>[NH3:10].[F:36][C:25]1[CH:26]=[C:27]([C:30]2[O:34][N:33]=[C:32]([CH3:35])[N:31]=2)[CH:28]=[CH:29][C:24]=1[N:20]1[CH2:21][CH2:22][CH:17]([CH2:16][CH:13]2[CH2:12][CH2:11][N:10]([CH:8]([CH3:9])[CH3:7])[CH2:15][CH2:14]2)[CH2:18][CH2:19]1

참가 물질

7

반응물 3

HCID 23676156Sodium t-butoxideHCID 574423175-(4-Bromo-3-fluorophenyl)-3-methyl-1,2,4-oxadiazoleHCID 688858081-(1-Methylethyl)-4-(4-piperidinylmethyl)piperidine

생성물 2

HCID 222AmmoniaHCID 115964821-[2-Fluoro-4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]-4-{[1-(1-methylethyl)-4-piperidinyl]methyl}piperidine수율 46.7%

시약·촉매·용매 2

HCID 119822622-(2'-Di-tert-butylphosphine)biphenylpalladium(II) acetate촉매HCID 1140Toluene용매

반응 조건

온도
80 °C

실험 절차

Sodium tert-butoxide (0.084 g) was added to a solution 1-(1-methylethyl)-4-(4-piperidinylmethyl)piperidine (may be prepared as described in Description 4) (0.156 g), 5-(4-bromo-3-fluorophenyl)-3-methyl-1,2,4-oxadiazole (may be prepared as described in Description 15) (0.150 g) and acetato(2′-di-tert-butylphosphino-1,1′-biphenyl-2-yl)palladium(II) (0.023 g) in toluene (10 ml). The reaction mixture was heated under argon at 80° C. overnight. After cooling to room temperature, the reaction mixture was passed through an SCX column (10 g, eluting with methanol [80 ml] then 2N NH3 in methanol [80 ml]) to afford the title compound (E14) (0.065 g). MS electrospray (+ion) 401 (MH+). 1H NMR δ (CDC13): 7.79 (1H, dd, J=2, 8 Hz), 7.73 (1H, dd, J=2, 13.6 Hz), 7.00 (1H, t, J=8.6 Hz), 3.62 (2H, m), 2.90 (2H, m), 2.84-2.69 (3H, m), 2.44 (3H, s), 2.12 (2H, m), 1.77 (2H, m), 1.69 (2H, m), 1.56 (1H, m), 1.42-1.22 (7H, m), 1.05 (6H, d)

후처리

  1. temperatureAfter cooling to room temperature
  2. washeluting with methanol [80 ml]

출처 및 근거

ORD 기록
ord-a8ebb9ad13a24428af87ae335f74adc1
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07638631B2

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