Methyl chloroformate → 2-(4,4-Difluoro-piperidine-1-carbonyl)-5-(1-isopropyl-piperidin-4-yloxy)-indole-1-carboxylic acid methyl ester

HRID 19845

反応式

HRID 19845 の反応式
[F:1][C:2]1([F:29])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[NH:11][C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:19][CH:20]2[CH2:25][CH2:24][N:23]([CH:26]([CH3:28])[CH3:27])[CH2:22][CH2:21]2)=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:40][O:41][C:42](Cl)=[O:43]>O1CCCC1.[Cl-].[Na+].O>[CH3:40][O:41][C:42]([N:11]1[C:12]2[C:17](=[CH:16][C:15]([O:19][CH:20]3[CH2:25][CH2:24][N:23]([CH:26]([CH3:27])[CH3:28])[CH2:22][CH2:21]3)=[CH:14][CH:13]=2)[CH:18]=[C:10]1[C:8]([N:5]1[CH2:6][CH2:7][C:2]([F:1])([F:29])[CH2:3][CH2:4]1)=[O:9])=[O:43]

参加物

6

反応物 3

HCID 6586Methyl chloroformateHCID 2733832Lithium HexamethyldisilazideHCID 11603838(4,4-Difluoropiperidin-1-yl)[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]methanone2 回

生成物 1

HCID 167394112-(4,4-Difluoro-piperidine-1-carbonyl)-5-(1-isopropyl-piperidin-4-yloxy)-indole-1-carboxylic acid methyl ester収率 15.7%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

A solution of (4,4-difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone (intermediate 1, 100 mg, 1.0 eq.), lithium bis-(trimethylsilyl)amide (1M solution in tetrahydrofuran, 271 ul, 1.1 eq.) and methylchloroformate (26 mg, 1.1 eq.) in tetrahydrofuran (2 mL) was stirred at room temperature for 48 h, then poured into brine, extracted with dichloromethane, dried over sodium sulfate, filtered, evaporated to dryness and purified on silica gel, eluting with a 98:2 to 97:3 gradient of dichloromethane/methanol, to yield 18 mg (15%) of the desired product as yellow oil. MS (m/e): 464.2 (MH+, 100%).

後処理

  1. extractionextracted with dichloromethane
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated to dryness
  5. custompurified on silica gel
  6. washeluting with a 98:2 to 97:3 gradient of dichloromethane/methanol

出典と根拠

ORDレコード
ord-0b28f7277bb243879e98cc1ec3c71219
出典データセット
uspto-grants-2010_06
特許番号
US07745479B2

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