Methanol → (R)-2-Methyl-1-oxo-1-(1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinolin-2(1H)-yl)propan-2-yl acetate

HRID 445279

反応式

HRID 445279 の反応式
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:12][CH2:11][NH:10]2)=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.[C:30]([O:33][C:34]([C:37](Cl)=[O:38])([CH3:36])[CH3:35])(=[O:32])[CH3:31].CO>C(Cl)Cl>[C:30]([O:33][C:34]([CH3:36])([CH3:35])[C:37](=[O:38])[N:10]1[CH2:11][CH2:12][C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C@H:9]1[C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:19])[F:20])=[CH:8][CH:7]=1)(=[O:32])[CH3:31]

参加物

6

反応物 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 1234962-Acetoxyisobutyroyl chloride2 回HCID 28293305(R)-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline

生成物 1

HCID 59536313(R)-2-Methyl-1-oxo-1-(1-(4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinolin-2(1H)-yl)propan-2-yl acetate

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of (R)-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (207 mg, 747 μmol, example 30 (step 1) and DIEA (130 μL, 747 μmol) in DCM (2.5 mL) was added 1-chlorocarbonyl-1-methylethyl acetate (119 μL, 821 μmol). The mixture was stirred at RT for 3 h. Then, 1-chlorocarbonyl-1-methylethyl acetate (50 μL) was added and the mixture was stirred at RT for 16 h. MeOH (1 mL) was added and the mixture was filtered. The filtrate was purified by preparative HPLC (0%-100% MeCN 0.1% TFA/water 0.1% TFA) to give the title compound in a solution of H2O 0.1% TFA and MeCN 0.1% TFA. The solvent was removed and saturated NaHCO3 (5 mL) was added. The mixture was extracted with EtOAc (2×30 mL). The combined organic extracts were dried over MgSO4, concentrated, and dried in vacuo to give the title compound as a white solid. MS (ESI, positive ion) m/z: 406 (M+H).

後処理

  1. stirringthe mixture was stirred at RT for 16 h
  2. filtrationthe mixture was filtered
  3. customThe filtrate was purified by preparative HPLC (0%-100% MeCN 0.1% TFA/water 0.1% TFA)

出典と根拠

ORDレコード
ord-1788a70662394664921c8942a9e49528
出典データセット
uspto-grants-2013_07
特許番号
US08476297B2

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