Sodium Bicarbonate → Methyl{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}[3-(trifluoromethyl)-5-vinylbenzyl]carbamate

HRID 217519

반응식

HRID 217519 반응식
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:11][O:12][C:13](=[O:50])[N:14]([CH2:37][C:38]1[CH:43]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:41]=[C:40]([CH:48]=O)[CH:39]=1)[CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=1[C:26]1[CH:31]=[C:30]([CH:32]([CH3:34])[CH3:33])[CH:29]=[CH:28][C:27]=1[O:35][CH3:36].[C:51]([O-])(O)=O.[Na+]>C1COCC1.C1(C)C=CC=CC=1.CCOC(C)=O>[CH3:11][O:12][C:13](=[O:50])[N:14]([CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:24])([F:25])[F:23])[CH:19]=[CH:18][C:17]=1[C:26]1[CH:31]=[C:30]([CH:32]([CH3:34])[CH3:33])[CH:29]=[CH:28][C:27]=1[O:35][CH3:36])[CH2:37][C:38]1[CH:39]=[C:40]([CH:48]=[CH2:51])[CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=1

참가 물질

7

반응물 3

HCID 516892Sodium BicarbonateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 11497822Methyl[3-formyl-5-(trifluoromethyl)benzyl]{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

생성물 1

HCID 11721070Methyl{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}[3-(trifluoromethyl)-5-vinylbenzyl]carbamate

시약·촉매·용매 3

HCID 1140Toluene용매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

실험 절차

A suspension of Ph3PCH3Br (53.4 mg, 0.15 mmol) in THF (500 μL) was cooled to 0° C. potassium bis(trimethylsilyl)amide (256 μL of a 0.5 M solution in toluene, 0.128 mmol) was added slowly and the reaction was kept at 0° C. After fifteen minutes, methyl[3-formyl-5-(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (24.2 mg, 0.043 mmol) (Example 40) was dissolved in THF (1 mL) and was added via cannula to the reaction which was then slowly warmed to room temperature. After fifteen minutes at room temperature, the reaction was diluted with EtOAc (30 mL), and poured into NaHCO3 (10 mL). The organic extract was washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 5% to 25% EtOAc/hexanes afforded methyl{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}[3-(trifluoromethyl)-5-vinylbenzyl]carbamate. Rf=0.42 (25% EtOAc/hexanes) LCMS=566.2 (M+1)+. 1H NMR (C6D6, 500 MHz, 70° C.) δ 7.68 (broad singlet, 1H), 7.36 (s, 1H), 7.34 (d, J=8.0 Hz, 1H), 7.15 (broad singlet, 1H), 7.10 (d, J=10.5 Hz, 1H), 7.03 (d, J=8.0 Hz, 1H), 7.01 (dd, J=8.5, 2.0 Hz, 1H), 6.81 (d, J=2.0 Hz, 1H), 6.54 (d, J=8.5 Hz, 1H), 6.32-6.27 (m, 1H), 5.40 (d, J=18 Hz, 1H), 4.97 (d, J=11 Hz, 1H), 4.37 (broad singlet, 2H), 4.04 (broad singlet, 2H), 3.34 (s, 3H), 3.20 (s, 3H), 2.69 (m, 1H), 1.12 (d, J=7.0 Hz, 6H).

후처리

  1. additionwas added slowly
  2. customwas kept at 0° C
  3. waitAfter fifteen minutes
  4. additionwas added via cannula to the reaction which
  5. waitAfter fifteen minutes at room temperature
  6. extractionThe organic extract
  7. washwas washed with brine (10 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by flash chromatography with 5% to 25% EtOAc/hexanes

출처 및 근거

ORD 기록
ord-560f0b7ca7184a58a5c17e85fa5a3f2b
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08193365B2

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