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 538000ノート

反応式

HRID 538000 の反応式
[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]

参加物

5

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-5759c8a148a843ffa2c347f4284d6b18
出典データセット
uspto-grants-2014_10
特許番号
US08865707B2

反応ノート

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