Benzyl Bromide → (S)-1-fluoro-3-(1-(4-fluorophenyl)-1-isocyano-2-phenylethyl)-5-(trifluoromethyl)benzene

HRID 238849

반응식

HRID 238849 반응식
[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([CH:12]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[N+:13]#[C-:14])[CH:3]=1.[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[OH-].[K+]>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:10])([F:11])[F:9])[CH:5]=[C:4]([C@@:12]([C:15]2[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=2)([N+:13]#[C-:14])[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:3]=1.[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:10])([F:11])[F:9])[CH:5]=[C:4]([C@:12]([C:15]2[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=2)([N+:13]#[C-:14])[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:3]=1

참가 물질

7

반응물 3

HCID 7498Benzyl BromideHCID 14797Potassium HydroxideHCID 59458753HCID 59458753, 화합물

생성물 2

HCID 59458487(S)-1-fluoro-3-(1-(4-fluorophenyl)-1-isocyano-2-phenylethyl)-5-(trifluoromethyl)benzene수율 42%HCID 59458629HCID 59458629, 화합물수율 42%

시약·촉매·용매 2

HCID 74236Tetrabutylammonium Bromide촉매HCID 1140Toluene용매

실험 절차

To a solution of 1-fluoro-3-((4-fluorophenyl)(isocyano)methyl)-5-(trifluoromethyl)benzene (234 mg, 0.79 mmol) in toluene (8 mL) was added tetrabutylammonium bromide (75 mg, 0.23 mmol) and benzyl bromide (0.185 mL, 1.56 mmol) followed by 50% KOH(aq) (2.5 mL). The reaction mixture was vigorously stirred for 3 minutes. The reaction mixture was transferred to a separatory funnel and washed with H2O (2.5 mL). The organic fraction was dried over Na2SO4, filtered through a pad of basic alumina and concentrated under reduced pressure. The residue was purified by chiral prep HPLC (Chiralcel OD-H column, 20×250 mm isocratic elution with isopropyl alcohol (10%) and heptane, 20 mL/min, monitoring at 254 nm) to give (R)-1-fluoro-3-(1-(4-fluorophenyl)-1-isocyano-2-phenylethyl)-5-(trifluoromethyl)benzene (RT=6.2 minutes, 128 mg, 42% yield) and (S)-1-fluoro-3-(1-(4-fluorophenyl)-1-isocyano-2-phenylethyl)-5-(trifluoromethyl)benzene (RT=7.8 minutes, 128 mg, 42% yield) as clear colorless oils. LCMS: RT=1.94 min [M−NC] 361.1 (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% acetonitrile/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); NMR: 400 MHz 1H (CDCl3) δ ppm 3.61 (d, J=13.18 Hz, 1H), 3.67 (d, J=13.18 Hz, 1H), 6.83 (d, J=7.47 Hz, 2H), 7.08 (t, J=8.57 Hz, 2H), 7.17-7.34 (m, 8H).

후처리

  1. customThe reaction mixture was transferred to a separatory funnel
  2. washwashed with H2O (2.5 mL)
  3. dry with materialThe organic fraction was dried over Na2SO4
  4. filtrationfiltered through a pad of basic alumina
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by chiral prep HPLC (Chiralcel OD-H column, 20×250 mm isocratic elution with isopropyl alcohol (10%) and heptane, 20 mL/min, monitoring at 254 nm)

출처 및 근거

ORD 기록
ord-2104d424b90b44a7bef7d8bd574e8893
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08642576B2

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