Toluene → tert-Butyl 3-cyclopropyl-4-fluorobenzylcarbamate

HRID 1093043노트

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HRID 1093043 반응식
[C:1]1([CH3:7])C=CC=C[CH:2]=1.Br[C:9]1[CH:10]=[C:11]([CH:21]=[CH:22][C:23]=1[F:24])[CH2:12][NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(B(O)O)CC1>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:7]1([C:9]2[CH:10]=[C:11]([CH:21]=[CH:22][C:23]=2[F:24])[CH2:12][NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:1][CH2:2]1

참가 물질

7

반응물 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 21961437[(3-Bromo-4-fluorophenyl)methyl]-carbamic acid tert-butyl ester

생성물 1

HCID 57905173tert-Butyl 3-cyclopropyl-4-fluorobenzylcarbamate수율 88%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 962Water용매2회

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온도
100 °C

실험 절차

Under N2, a toluene (4.70 mL)/water (0.235 mL) solution of tert-butyl 3-bromo-4-fluorobenzylcarbamate (0.300 g, 0.986 mmol) was treated with potassium phosphate tribasic (0.733 g, 3.45 mmol), cyclopropylboronic acid (0.110 g, 1.282 mmol), and tricyclohexenylphosphene (0.028 g, 0.099 mmol) in was added palladium(II) acetate (0.011 g, 0.049 mmol). The reaction was stirred at 100° C. for 3 h. The solution was diluted with water (15 mL) then extracted with ethyl acetate (2×15 mL). The organic extracts were combined, washed with brine (20 mL), then dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography (Biotage flash chromatography system; 60 g SiO2; 0-20% ethyl acetate:hexane over 900 mL) to give the title compound as a white crystalline solid (0.230 g, 88% yield). 1H NMR (500 MHz, CDCl3) δ: 6.98-7.05 (1 H, m), 6.90-6.97 (1 H, m), 6.79 (1 H, dd, J=7.02, 1.53 Hz), 4.75 (1 H, brs), 4.21 (2 H, d, J=5.49 Hz), 2.02-2.09 (1 H, m), 1.45 (9 H, s), 0.93-1.01 (2 H, m), 0.66-0.75 (2 H, m).

후처리

  1. extractionthen extracted with ethyl acetate (2×15 mL)
  2. washwashed with brine (20 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (Biotage flash chromatography system; 60 g SiO2; 0-20% ethyl acetate:hexane over 900 mL)

출처 및 근거

ORD 기록
ord-0233b4f045794367a37796fd52eecf5f
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129398B2

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