Triphenylphosphine → (+/-)-4-{1-[3,5-Difluoro-4-(4-trifluoromethyl-pyrazol-1-yl)-phenoxy]-butyl}-benzoic acid ethyl ester

HRID 1520970노트

반응식

HRID 1520970 반응식
[F:1][C:2]1[CH:3]=[C:4]([OH:18])[CH:5]=[C:6]([F:17])[C:7]=1[N:8]1[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[N:9]1.O[CH:20]([C:24]1[CH:34]=[CH:33][C:27]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:26][CH:25]=1)[CH2:21][CH2:22][CH3:23].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCCC=[N+]=[N-])=O)=NC([O-])=O>O1CCCC1>[CH2:31]([O:30][C:28](=[O:29])[C:27]1[CH:33]=[CH:34][C:24]([CH:20]([O:18][C:4]2[CH:5]=[C:6]([F:17])[C:7]([N:8]3[CH:12]=[C:11]([C:13]([F:15])([F:16])[F:14])[CH:10]=[N:9]3)=[C:2]([F:1])[CH:3]=2)[CH2:21][CH2:22][CH3:23])=[CH:25][CH:26]=1)[CH3:32]

참가 물질

6

반응물 4

HCID 11776TriphenylphosphineHCID 67981039Ethyl 4-(1-hydroxybutyl)benzoate2회HCID 681573243,5-Difluoro-4-(4-trifluoromethyl-pyrazol-1-yl)-phenolHCID 86669100Diazopropyl azodicarboxylate

생성물 1

HCID 68178668(+/-)-4-{1-[3,5-Difluoro-4-(4-trifluoromethyl-pyrazol-1-yl)-phenoxy]-butyl}-benzoic acid ethyl ester수율 100.7%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

3,5-Difluoro-4-(4-trifluoromethyl-pyrazol-1-yl)-phenol (230 mg, 0.871 mmol) was combined with ethyl 4-(1-hydroxybutyl)benzoate (see Intermediate 5) (194 mg, 0.871 mmol) and dissolved in anhydrous tetrahydrofuran (4 mL). Triphenylphosphine (457 mg, 1.74 mmol) was added followed by diazopropyl azodicarboxylate (0.451 mL, 2.18 mmol). This was stirred at room temperature as a yellow solution. At 17 h, the reaction was concentrated. Purification by silica gel flash chromatography (ethyl acetate in heptane) gave impure (+/−)-4-{1-[3,5-difluoro-4-(4-trifluoromethyl-pyrazol-1-yl)-phenoxy]-butyl}-benzoic acid ethyl ester (0.411 g) as a clear oil. 1H NMR (400 MHz, CDCl3, δ): 8.06 (d, J=8.2 Hz, 2H) 7.93 (s, 1H) 7.82 (s, 1H) 7.39 (d, J=8.4 Hz, 2H) 6.54 (d, J=9.4 Hz, 2H) 5.15 (dd, J=7.6, 5.3 Hz, 1H) 4.39 (q, J=7.2 Hz, 2H) 1.96-2.10 (m, 1H) 1.77-1.91 (m, 1H) 1.19-1.61 (m, 5H) 0.98 (t, J=7.3 Hz, 3H); MS (M+1): 469.3.

후처리

  1. concentrationthe reaction was concentrated
  2. customPurification by silica gel flash chromatography (ethyl acetate in heptane)

출처 및 근거

ORD 기록
ord-cd72e70f76184dcaa15d975231600386
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073871B2

반응 노트

불러오는 중…