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Sodium hydride → tert-butyl (2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-[2-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]piperidine-1-carboxylate

HRID 1644481
ノート
印刷プレビュー

反応式

HRID 1644481 の反応式
[Si:1]([O:8][C@H:9]1[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C@@H:12]([CH2:22][CH2:23]O)[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.CS(Cl)(=O)=O.[O:39]=[C:40]1[NH:45][C:44]2[CH:46]=[C:47]([C:50]#[N:51])[CH:48]=[CH:49][C:43]=2[O:42][CH2:41]1.[H-].[Na+].S([O-])(=O)(=O)C>C(Cl)Cl.CN(C=O)C>[Si:1]([O:8][C@H:9]1[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:19])[CH3:20])=[O:16])[C@@H:12]([CH2:22][CH2:23][N:45]2[C:44]3[CH:46]=[C:47]([C:50]#[N:51])[CH:48]=[CH:49][C:43]=3[O:42][CH2:41][C:40]2=[O:39])[CH2:11][CH2:10]1)([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:3])[CH3:2]
参加物実験手順後処理出典と根拠反応ノート

参加物

9

反応物 6

HCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 85257MethanesulfonateHCID 106548133-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile2 回HCID 66774126tert-butyl(2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-(2-hydroxyethyl)piperidine-1-carboxylate2 回

生成物 1

HCID 66774834tert-butyl (2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-[2-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]piperidine-1-carboxylate

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of tert-butyl(2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-(2-hydroxyethyl)piperidine-1-carboxylate (Intermediate 187, 1.27 g) in methylene chloride (15 mL) at 0° C. were added diisopropylethylamine (1.2 mL) and methanesulfonyl chloride (0.50 mL). At the same time in a separate flask, to a solution of 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carbonitrile (Intermediate 60) (0.66 g) in DMF (8 mL) at 0° C. was added 60% suspension in oil of NaH (0.25 g). After 30 minutes, the mesylate solution was diluted with methylene chloride, washed with NaHCO3 and brine, dried over sodium sulfate and concentrated. This residue was dissolved in DMF (5 mL) and added to the sodium salt of Intermediate 60. The reaction was stirred over the weekend, diluted with ethyl acetate, washed with NaHCO3 and brine, dried over sodium sulfate and concentrated to give the product.

後処理

  1. washwashed with NaHCO3 and brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. dissolutionThis residue was dissolved in DMF (5 mL)
  5. additionadded to the sodium salt of Intermediate 60
  6. additiondiluted with ethyl acetate
  7. washwashed with NaHCO3 and brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customto give the product

出典と根拠

ORDレコード
ord-a6200cc78f294e6d8c667a10483ac328
出典データセット
uspto-grants-2012_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08124602B2

反応ノート

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