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Citric Acid → 5-(3,3-dimethyl-but-1-ynyl)-3-[((1R)-4-methyl-cyclohex-3-enecarbonyl)-(1-oxa-spiro[2.5]oct-6-yl)-amino]thiophene-2-carboxylic acid methyl ester

HRID 1053491
ノート
印刷プレビュー

反応式

HRID 1053491 の反応式
[Cl-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[CH3:9][O:10][C:11]([C:13]1[S:14][C:15]([C:35]#[C:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[CH:16][C:17]=1[N:18]([C:26]([C@@H:28]1[CH2:33][CH2:32][C:31]([CH3:34])=[CH:30][CH2:29]1)=[O:27])[CH:19]1[CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]1)=[O:12].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O.C1COCC1>[CH3:9][O:10][C:11]([C:13]1[S:14][C:15]([C:35]#[C:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[CH:16][C:17]=1[N:18]([C:26]([C@@H:28]1[CH2:33][CH2:32][C:31]([CH3:34])=[CH:30][CH2:29]1)=[O:27])[CH:19]1[CH2:20][CH2:21][C:22]2([O:25][CH2:2]2)[CH2:23][CH2:24]1)=[O:12]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 311Citric AcidHCID 24758Sodium hydrideHCID 197819Trimethyloxosulphonium chlorideHCID 679837405-(3,3-dimethyl-but-1-ynyl)-3-[((1R)-4-methyl-cyclohex-3-enecarbonyl)-(4-oxo-cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl ester

生成物 1

HCID 866989545-(3,3-dimethyl-but-1-ynyl)-3-[((1R)-4-methyl-cyclohex-3-enecarbonyl)-(1-oxa-spiro[2.5]oct-6-yl)-amino]thiophene-2-carboxylic acid methyl ester
収率 70%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

Trimethylsulfoxonium chloride (79 mg, 0.62 mmol) in DMSO (1.5 mL) was treated with sodium hydride (21 mg, 60% oil dispersion, 0.53 mmol) and stirred at ambient temperature for 10 min. 5-(3,3-Dimethyl-but-1-ynyl)-3-[((1R)-4-methyl-cyclohex-3-enecarbonyl)-(4-oxo-cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl ester 507 in THF (1 mL+0.5 mL) was added dropwise and the reaction mixture was stirred for 45 min. The orange solution was treated with 5% citric acid until pH 3 and partitioned between water and ethyl acetate. The organic layer was separated and the aqueous was extracted again with ethyl acetate. The combined organics were washed with 5% LiCl, water and brine, and dried over sodium sulfate. After filtration and concentration, the residue was purified by flash chromatography (20-75% EtOAc:hexanes) to afford 0.134 g (70% yield) of 5-(3,3-dimethyl-but-1-ynyl)-3-[((1R)-4-methyl-cyclohex-3-enecarbonyl)-(1-oxa-spiro[2.5]oct-6-yl)-amino]-thiophene-2-carboxylic acid methyl ester 508 as a white powder.

後処理

  1. stirringthe reaction mixture was stirred for 45 min
  2. custompartitioned between water and ethyl acetate
  3. customThe organic layer was separated
  4. extractionthe aqueous was extracted again with ethyl acetate
  5. washThe combined organics were washed with 5% LiCl, water and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationAfter filtration and concentration
  8. customthe residue was purified by flash chromatography (20-75% EtOAc:hexanes)

出典と根拠

ORDレコード
ord-527aac3c98fb4e5298b35d546181d7dc
出典データセット
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09393256B2

反応ノート

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