Triethylamine → HCID 58974989、化合物

HRID 737060ノート

反応式

HRID 737060 の反応式
C(O[C:6]([N:8]1[CH2:11][CH:10]([C:12]([OH:14])=O)[CH2:9]1)=[O:7])(C)(C)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].[C:21]1([C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:29]([S:36]([C:39]3[CH:47]=[CH:46][C:42](C(O)=O)=[CH:41][CH:40]=3)(=[O:38])=[O:37])[CH:28]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.N1CC(CO)C1.C(N(CC)CC)C.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C1COCC1.ClCCl>[OH:14][CH2:12][CH:10]1[CH2:9][N:8]([C:6]([C:42]2[CH:41]=[CH:40][C:39]([S:36]([N:29]3[C:30]4[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=4)[C:27]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[CH:28]3)(=[O:38])=[O:37])=[CH:47][CH:46]=2)=[O:7])[CH2:11]1

参加物

9

反応物 6

HCID 8471TriethylamineHCID 124335Benzotriazol-1-yloxy-tris(dimethylamino)phosphoniumHCID 27559811-Boc-Azetidine-3-carboxylic acidHCID 13400658(Azetidin-3-yl)methanolHCID 21226445Aluminium lithium hydrideHCID 589751414-(3-Phenyl-indole-1-sulfonyl)-benzoic acid

生成物 1

HCID 58974989HCID 58974989、化合物収率 35.3%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

Dissolve azetidine-1,3-dicarboxylic acid mono-tert-butyl ester (300 mg, 1.50 mmol.) in THF (5.0 mL) and treat with lithium aluminum hydride (1.0M in ether, 3.0 mL, 3.0 mmol). Stir for 18 hours, quench with 3.0 mL of 1.0M NaOH, dilute with ether, filter through celite and evaporate. Treat the resulting 3-hydroxymethyl-azetidine-1-carboxylic acid tert-butyl ester with 10 mL of trifluoroacetic acid for 20 minutes an evaporate. Use this material without further purification. Combine 4-(3-Phenyl-indole-1-sulfonyl)-benzoic acid (100 mg, 0.26 mmol) and the resulting azetidin-3-yl-methanol in dichloromethane (1.0 mL) and triethylamine (0.100 mL, 0.717 mmol, excess) and add benzotriazol-1-yloxytris(dimethylamino)phosphonium hexfluorophosphate (BOP Reagent) (150 mg, 0.33 mmol, excess) at room temperature. Stir for 30 minutes, evaporate and load entire reaction directly onto pre-packed silica gel column and purify by flash column chromatography (EtOAc/Hexanes) to give 41 mg of (3-Hydroxymethyl-azetidin-1-yl)-[4-(3-phenyl-indole-1-sulfonyl)-phenyl]-methanone as a white solid (35%). LRMS: MH+ 447.2.

後処理

  1. customquench with 3.0 mL of 1.0M NaOH
  2. additiondilute with ether
  3. filtrationfilter through celite
  4. customevaporate
  5. additionTreat the resulting 3-hydroxymethyl-azetidine-1-carboxylic acid tert-butyl ester with 10 mL of trifluoroacetic acid for 20 minutes an evaporate
  6. customwithout further purification
  7. stirringStir for 30 minutes
  8. customevaporate
  9. customreaction directly onto pre-packed silica gel column
  10. custompurify by flash column chromatography (EtOAc/Hexanes)

出典と根拠

ORDレコード
ord-69b27a67a28349cda5c63e723884e0a8
出典データセット
uspto-grants-2009_09
特許番号
US07595339B2

反応ノート

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