Tetrabutylammonium Fluoride Trihydrate → (3R,4R)-3-[(Cyclopropyl-phenylacetyl-amino)-methyl]-4-(isopropylamino-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158441ノート

反応式

HRID 1158441 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:24]([CH3:26])[CH3:25])C(OCC[Si](C)(C)C)=O)[C@H:10]([CH2:27][N:28]([CH:38]2[CH2:40][CH2:39]2)[C:29](=[O:37])[CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>CC#N>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][NH:14][CH:24]([CH3:25])[CH3:26])[C@H:10]([CH2:27][N:28]([CH:38]2[CH2:39][CH2:40]2)[C:29](=[O:37])[CH2:30][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

参加物

4

反応物 2

HCID 11726816Tetrabutylammonium Fluoride TrihydrateHCID 59512347(3R,4S)-3-[(Cyclopropyl-phenylacetyl-amino)-methyl]-4-{[isopropyl-(2-trimethylsilanyl-ethoxycarbonyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 59512261(3R,4R)-3-[(Cyclopropyl-phenylacetyl-amino)-methyl]-4-(isopropylamino-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a solution of (3R,4S)-3-[(cyclopropyl-phenylacetyl-amino)-methyl]-4-{[isopropyl-(2-trimethylsilanyl-ethoxycarbonyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (2.55 g, 4.44 mmol) in CH3CN (30 mL) is added tetrabutylammonium fluoride trihydrate (4.34 g, 13.33 mmol) under a nitrogen atmosphere. The reaction mixture is stirred overnight at reflux. The solvent is removed under vacuum and Water and CH2Cl2 are added, the layers are separated and the aqueous one extracted twice with CH2Cl2. The combined organic extracts are dried (Na2SO4), and the solvent is removed in vacuo. The crude product is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH/NH4OH 98:2:1) to give the title product. TLC, Rf (CH2Cl2/MeOH/NH4OH 98:2:1)=0.11. MS (LC-MS): 430.2 [M+H]+; tR (HPLC, C18 column, 20-100% CH3CN/H2O/16 min, 100% CH3CN/1.5 min, CH3CN and H2O containing 0.1% TFA, flow: 1 mL/min): 3.90 min.

後処理

  1. temperatureat reflux
  2. customThe solvent is removed under vacuum and Water and CH2Cl2
  3. additionare added
  4. customthe layers are separated
  5. extractionthe aqueous one extracted twice with CH2Cl2
  6. dry with materialThe combined organic extracts are dried (Na2SO4)
  7. customthe solvent is removed in vacuo
  8. customThe crude product is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH/NH4OH 98:2:1)

出典と根拠

ORDレコード
ord-6e29d67b35a7497dad7c002e31e38f03
出典データセット
uspto-grants-2010_10
特許番号
US07807709B2

反応ノート

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