Imidazole → (2S,3R,4S,5S,6R)-6-[(tert-butyl(dimethyl)silyl)oxymethyl]-2-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol

HRID 1055534Notes

Reaction equation

HRID 1055534 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([O:19][CH3:20])[C@H:13]([OH:14])[C@@H:12]([OH:15])[C@H:11]([OH:16])[C@@H:10]([CH2:17][OH:18])[O:9]2)=[CH:4][C:3]=1[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=1.N1C=CN=C1.[Si:38](Cl)([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39].C(=O)(O)[O-].[Na+]>ClCCl.CN(C)C1C=CN=CC=1>[Si:38]([O:18][CH2:17][C@H:10]1[O:9][C@:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:30])[F:31])=[CH:24][CH:23]=3)[CH:4]=2)([O:19][CH3:20])[C@H:13]([OH:14])[C@@H:12]([OH:15])[C@@H:11]1[OH:16])([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39]

Participants

7

Reactant 4

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 516892Sodium BicarbonateHCID 68015110(2S,3R,4S,5S,6R)-2-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol

Product 1

HCID 86685138(2S,3R,4S,5S,6R)-6-[(tert-butyl(dimethyl)silyl)oxymethyl]-2-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triolYield 110.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (2S,3R,4S,5S,6R)-2-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-6-(hydroxymethyl)-2-methoxy-tetrahydropyran-3,4,5-triol 15h (1.0 g, 2.09 mmol) in dichloromethane (15 mL) were added imidazole (0.57 g, 8.39 mmol), tert-butyldimethylsilyl chloride (0.63 g, 4.19 mmol) and 4-dimethylaminopyridine (26 mg, 0.21 mmol) in turn at 0° C. The mixture was warmed up to room temperature and stirred for 1.5 hours. The reaction mixture was adjusted with saturated aqueous sodium bicarbonate to pH 7 and partitioned. The aqueous layer was extracted with dichloromethane (20 mL×2). The combined organic layers were washed with saturated brine (20 mL×2), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to give the title compound 15i as yellow oil (1.37 g, 100%). This material was not further purified.

Workup

  1. custompartitioned
  2. extractionThe aqueous layer was extracted with dichloromethane (20 mL×2)
  3. washThe combined organic layers were washed with saturated brine (20 mL×2)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-8bfe2e2ca1c04d729147e546ab8f3145
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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