1,1'-Carbonyldiimidazole → ethyl 2-((1R)-1-{2-[(benzyloxy)amino]-2-oxoethyl}-4-cyclohexylbutyl)-1,3-oxazole-4-carboxylate

HRID 1279861ノート

反応式

HRID 1279861 の反応式
FC(F)(F)C(O)=O.[CH:8]1([CH2:14][CH2:15][CH2:16][C@@H:17]([C:22]2[O:23][CH:24]=[C:25]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[N:26]=2)[CH2:18][C:19]([OH:21])=O)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH2:45]([O:52][NH2:53])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.C(N(CC)C(C)C)(C)C>O1CCCC1.C(OCC)(=O)C>[CH2:45]([O:52][NH:53][C:19](=[O:21])[CH2:18][C@H:17]([C:22]1[O:23][CH:24]=[C:25]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[N:26]=1)[CH2:16][CH2:15][CH2:14][CH:8]1[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1)[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1

参加物

7

反応物 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 102312Benzyloxyamine hydrochlorideHCID 69778281(3R)-6-Cyclohexyl-3-[4-(ethoxycarbonyl)-1,3-oxazol-2-yl]hexanoic acid trifluoroacetate

生成物 1

HCID 60077661ethyl 2-((1R)-1-{2-[(benzyloxy)amino]-2-oxoethyl}-4-cyclohexylbutyl)-1,3-oxazole-4-carboxylate収率 86.6%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of (3R)-6-cyclohexyl-3-[4-(ethoxycarbonyl)-1,3-oxazol-2-yl]hexanoic acid trifluoroacetate (Preparation 63) (1.66 g, 3.68 mmol), 1,1′-carbonyldiimidazole (0.80 g, 4.93 mmol), O-benzylhydroxylamine hydrochloride (1.57 g, 9.84 mmol) and N,N-diisopropylethylamine (1.71 ml, 9.82 mmol) in anhydrous tetrahydrofuran (10 ml) was stirred at room temperature for 72 hours. The mixture was diluted with ethyl acetate (50 ml) and washed sequentially with a saturated solution of sodium hydrogen carbonate, aqueous citric acid solution (10% w/v) and brine, dried over anhydrous magnesium sulphate, filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol (98:2) then further purified by column chromatography on silica gel eluting with ethyl acetate:pentane (50:50) to afford the title compound as an orange oil (1.41 g)

後処理

  1. washwashed sequentially with a saturated solution of sodium hydrogen carbonate, aqueous citric acid solution (10% w/v) and brine
  2. dry with materialdried over anhydrous magnesium sulphate
  3. filtrationfiltered
  4. customthe solvent removed under reduced pressure
  5. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol (98:2)
  6. customthen further purified by column chromatography on silica gel eluting with ethyl acetate:pentane (50:50)

出典と根拠

ORDレコード
ord-52d32cd5353d495a8eda5ae5cdb45fe3
出典データセット
uspto-grants-2002_09
特許番号
US06448278B2

反応ノート

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