Potassium tert-butoxide → methyl 4'-methoxy-2''-{[(6S)-6-(2-methoxyphenyl)-2-oxo-1,3-oxazinan-3-yl]methyl}-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

HRID 538000노트

반응식

HRID 538000 반응식
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C@H:9]1[O:14][C:13](=[O:15])[NH:12][CH2:11][CH2:10]1.[CH3:16]C([O-])(C)C.[K+].Br[CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[C:34]1[CH:35]=[C:36]([C:42]2[CH:47]=[CH:46][C:45]([C:48]([O-:50])=[O:49])=[CH:44][C:43]=2[CH3:51])[CH:37]=[CH:38][C:39]=1[O:40][CH3:41]>CN(C=O)C>[CH3:41][O:40][C:39]1[CH:38]=[CH:37][C:36]([C:42]2[CH:47]=[CH:46][C:45]([C:48]([O:50][CH3:16])=[O:49])=[CH:44][C:43]=2[CH3:51])=[CH:35][C:34]=1[C:25]1[CH:26]=[CH:27][C:28]([C:30]([F:32])([F:33])[F:31])=[CH:29][C:24]=1[CH2:23][N:12]1[CH2:11][CH2:10][C@@H:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[O:14][C:13]1=[O:15]

참가 물질

5

반응물 3

HCID 23665647Potassium tert-butoxideHCID 68997782(6S)-6-(2-methoxyphenyl) 1,3-oxazinan-2-oneHCID 866261472''-(Bromomethyl)-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

생성물 1

HCID 24740082methyl 4'-methoxy-2''-{[(6S)-6-(2-methoxyphenyl)-2-oxo-1,3-oxazinan-3-yl]methyl}-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

To a solution of (6S)-6-(2-methoxyphenyl)-1,3-oxazinan-2-one (31.6 mg, 0.152 mmol) in DMF (1.5 mL) was added t-BuOK (16.5 mg, 0.144 mmol). The reaction was stirred for 15 minutes, then a solution of 2″-(bromomethyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (75 mg, 0.152 mmol) in DMF (15 mL) was added via cannula. The reaction was stirred at room temperature for 1 hour, and then quenched with saturated NH4Cl solution (10 mL), diluted with EtOAc (20 mL), washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography (10 to 50% EtOAc/hexanes) to afford methyl 4′-methoxy-2″-{[(6S)-6-(2-methoxyphenyl)-2-oxo-1,3-oxazinan-3-yl]methyl}-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate LCMS=619.8 (M+1)+. 1H NMR (CDCl3, 500 MHz, rotamers present) δ 7.78-7.94 (m, 2H), 7.68 (s, 1H), 7.60 (t, J=9.0 Hz, 1H), 7.25-7.44 (m, 5H), 6.79-7.15 (m, 4H), 5.58 (dd, J=9.2, 2.5 Hz), 5.32 (dd, J=9.2, 2.5 Hz), 4.76 (d, J=15.3 Hz, 1H), 4.57 (d, J=15.3 Hz), 4.48 (d, J=15.6 Hz), 3.92 (s, 3H), 3.86 (s), 3.84 (s), 3.80 (s), 3.65 (s), 2.88-3.16 (m, 2H), 2.35 (s), 2.32 (s), 1.85-2.20 (m, 2H).

후처리

  1. stirringThe reaction was stirred at room temperature for 1 hour
  2. customquenched with saturated NH4Cl solution (10 mL)
  3. additiondiluted with EtOAc (20 mL)
  4. washwashed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (10 to 50% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-5759c8a148a843ffa2c347f4284d6b18
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08865707B2

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