Pyridine → (S)-2-(tert-butoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propyl 4-methylbenzenesulfonate

HRID 451976ノート

反応式

HRID 451976 の反応式
[OH:1][CH2:2][C@@H:3]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:4][C@H:5]1[CH2:10][CH2:9][CH2:8][O:7][CH2:6]1.N1C=CC=CC=1.[S:25](Cl)([C:28]1[CH:34]=[CH:33][C:31]([CH3:32])=[CH:30][CH:29]=1)(=[O:27])=[O:26]>C(Cl)Cl.CCOC(C)=O>[CH3:32][C:31]1[CH:33]=[CH:34][C:28]([S:25]([O:1][CH2:2][C@@H:3]([NH:11][C:12]([O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:18])[CH2:4][C@H:5]2[CH2:10][CH2:9][CH2:8][O:7][CH2:6]2)(=[O:27])=[O:26])=[CH:29][CH:30]=1

参加物

6

反応物 3

HCID 1049Pyridine2 回HCID 73974-Toluenesulfonyl chloride2 回HCID 58011540tert-Butyl ((S)-1-hydroxy-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-yl)carbamate

生成物 1

HCID 58011568(S)-2-(tert-butoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propyl 4-methylbenzenesulfonate収率 75%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

The above crude product tert-butyl (S)-1-hydroxy-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamate was dissolved in anhydrous DCM (22 mL). To this solution was added pyridine (2 mL) and TsCl (1.230 g, 6.45 mmol). After stirred at rt for 4 hr, another batch of pyridine (3 mL) and TsCl (0.700 g, 3.67 mmol) was added and stirred for another 12 hr. The reaction mixture was diluted with EtOAc (80 mL), washed with 1 N HCl (75 mL), followed by H2O (2×30 mL), saturated aq. NaHCO3, brine, and dried over anhydrous Na2SO4, and filtered, and concentrated under reduced pressure. The resulted slurry was purified through flash chromatography on silica gel (eluted with gradient system: 0-35% EtOAc in hexane) to afford (S)-2-(tert-butoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propyl 4-methylbenzenesulfonate, 670 mg, yield 75% for two steps. MS ESI +ve m/z 436 (M+Na).

後処理

  1. stirringstirred for another 12 hr
  2. washwashed with 1 N HCl (75 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulted slurry was purified through flash chromatography on silica gel (eluted with gradient system: 0-35% EtOAc in hexane)

出典と根拠

ORDレコード
ord-918198197e9e4f3cac5b1090e2ddab72
出典データセット
uspto-grants-2013_07
特許番号
US08487108B2

反応ノート

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