Water → (S)-tert-butyl 3-((3'-(((3-(2-methoxy-2-oxoethyl)-2,3-dihydrobenzofuran-6-yl)oxy)methyl)-2,6-dimethylbiphenyl-4-yl)oxy)azetidine-1-carboxylate

HRID 2280660ノート

反応式

HRID 2280660 の反応式
CS([O:5][CH:6]1[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7]1)(=O)=O.O[C:18]1[CH:23]=[C:22]([CH3:24])[C:21]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([CH2:31][O:32][C:33]3[CH:46]=[CH:45][C:36]4[C@H:37]([CH2:40][C:41]([O:43][CH3:44])=[O:42])[CH2:38][O:39][C:35]=4[CH:34]=3)[CH:26]=2)=[C:20]([CH3:47])[CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O>[CH3:44][O:43][C:41](=[O:42])[CH2:40][C@H:37]1[C:36]2[CH:45]=[CH:46][C:33]([O:32][CH2:31][C:27]3[CH:26]=[C:25]([C:21]4[C:22]([CH3:24])=[CH:23][C:18]([O:5][CH:6]5[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7]5)=[CH:19][C:20]=4[CH3:47])[CH:30]=[CH:29][CH:28]=3)=[CH:34][C:35]=2[O:39][CH2:38]1

参加物

6

反応物 4

HCID 962WaterHCID 10796Cesium carbonateHCID 10753243Tert-butyl 3-(methanesulfonyloxy)azetidine-1-carboxylateHCID 57414918(S)-methyl 2-(6-((4'-hydroxy-2',6'-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate

生成物 1

HCID 89701788(S)-tert-butyl 3-((3'-(((3-(2-methoxy-2-oxoethyl)-2,3-dihydrobenzofuran-6-yl)oxy)methyl)-2,6-dimethylbiphenyl-4-yl)oxy)azetidine-1-carboxylate収率 50%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

tert-Butyl 3-((methylsulfonyl)oxy)azetidine-1-carboxylate 14a (100 mg, 0.40 mmol, prepared by a method disclosed in PCT patent application WO2011097958”), (S)-methyl 2-(6-((4′-hydroxy-2′,6′-dimethylbiphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetate 3 h (80 mg, 0.19 mmol) and cesium carbonate (130 mg, 0.40 mmol) were dissolved in 10 mL of N,N-dimethylformamide. The reaction solution was heated to 80° C. and stirred for 12 hours. The resulting solution was mixed with 10 mL of water, and extracted with ethyl acetate (30 mL×2). The combined organic extracts were washed with saturated sodium chloride solution (30 mL), dried with anhydrous magnesium sulphate, and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography with elution system B to obtain the title compound (S)-tert-butyl 3-((3′-(((3-(2-methoxy-2-oxoethyl)-2,3-dihydrobenzofuran-6-yl)oxy)methyl)-2,6-dimethylbiphenyl-4-yl)oxy)azetidine-1-carboxylate 14b (60 mg, yield 50.0%) as a colorless oil.

後処理

  1. extractionextracted with ethyl acetate (30 mL×2)
  2. washThe combined organic extracts were washed with saturated sodium chloride solution (30 mL)
  3. dry with materialdried with anhydrous magnesium sulphate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography with elution system B

出典と根拠

ORDレコード
ord-e9cae0ba0cb741499bc3662ab3f10865
出典データセット
uspto-grants-2015_09
特許番号
US09139548B2

反応ノート

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