Imidazole → (1R,2S,3S,4R,5S)-3,4-dibenzyloxy-1-[(tert-butyl(dimethyl)silyl)oxymethyl]-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-2-ol

HRID 1055613Notes

Reaction equation

HRID 1055613 reaction equation
[CH2:1]([O:8][C@@H:9]1[C@@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@:14]2([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([CH2:32][C:33]4[CH:38]=[CH:37][C:36]([O:39][CH2:40][CH3:41])=[CH:35][CH:34]=4)[CH:26]=3)[O:24][C@@:11]([CH2:42][OH:43])([CH2:12][O:13]2)[C@H:10]1[OH:44])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si:45](Cl)([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46].N1C=CN=C1.[Na]>ClCCl.CN(C)C1C=CN=CC=1>[CH2:1]([O:8][C@@H:9]1[C@@H:15]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C@:14]2([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([CH2:32][C:33]4[CH:34]=[CH:35][C:36]([O:39][CH2:40][CH3:41])=[CH:37][CH:38]=4)[CH:26]=3)[O:24][C@@:11]([CH2:42][O:43][Si:45]([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46])([CH2:12][O:13]2)[C@H:10]1[OH:44])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 5360545SodiumHCID 118391141(1S,2S,3S,4R,5S)-3,4-dibenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octan-2-ol

Product 1

HCID 131736403(1R,2S,3S,4R,5S)-3,4-dibenzyloxy-1-[(tert-butyl(dimethyl)silyl)oxymethyl]-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-2-olYield 115%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (1S,2S,3S,4R,5S)-3,4-dibenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octan-2-ol 28d (11.68 g, 18.9 mmol) in dichloromethane (40 mL) were added tert-butyldimethylsilyl chloride (3.4 g, 22.68 mmol), imidazole (2.57 g, 37.8 mmol) and a catalytic amount of 4-dimethylaminopyridine in turn at 0° C. The mixture was stirred at room temperature for 30 min and adjusted with saturated aqueous sodium bicarnonate till pH becomes 7. The resulting mixture was extracted with dichloromethane (50 mL×3). The combined organic phases were washed with saturated aqueous sodium chloride (30 mL×2), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to give the title compound 28e as a white solid (15.9 g, 100%). The crude product was used for next step without further purification.

Workup

  1. customat 0° C
  2. extractionThe resulting mixture was extracted with dichloromethane (50 mL×3)
  3. washThe combined organic phases were washed with saturated aqueous sodium chloride (30 mL×2)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-0b0d6c723b4e40b6a79bddbb595a4ff2
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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