Benzyl Bromide → HCID 131736379, compound

HRID 1055498Notes

Reaction equation

HRID 1055498 reaction equation
[H-].[Na+].[Si:3]([O:10][CH2:11][C@H:12]1[O:17][C@:16]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH3:36])=[CH:30][CH:29]=3)[CH:21]=2)([O:18][CH3:19])[C@H:15]([OH:37])[C@@H:14]([OH:38])[C@@H:13]1[OH:39])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].[CH2:40](Br)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>O1CCCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:6]([Si:3]([CH3:5])([CH3:4])[O:10][CH2:11][C@@H:12]1[C@@H:13]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C@H:14]([O:38][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@@H:15]([O:37][CH2:16][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C@@:16]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH3:36])=[CH:30][CH:29]=3)[CH:21]=2)([O:18][CH3:19])[O:17]1)([CH3:9])([CH3:7])[CH3:8]

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 131736380HCID 131736380, compound

Product 1

HCID 131736379HCID 131736379, compoundYield 86.9%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of sodium hydride (65.4 g, 1.627 mol, 60% dispersion in Mineral oil) in anhydrous tetrahydrofuran (100 mL) was added dropwise a solution of (2S,3R,4S,5S,6R)-6-[(tert-butyl (dimethyl)silyl)oxymethyl]-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-2-methoxy-tetrahydropyran-3,4,5-triol 1e (150 g, 0.271 mol) in anhydrous tetrahydrofuran (800 mL) at 0° C. The mixture was stirred at 0° C. for 1 hour and then allowed to warm up to room temperature. After benzyl bromide (113 mL, 951.84 mmol) and tetrabutylammonium iodide (3.91 g, 10.6 mmol) were added in turn, the mixture was stirred at 40° C. for 12 hours and cooled to 0° C., and then quenched with 50 mL of water. Most of the solvent was removed in vacuo. To the residue was added 200 mL of water. The resulting mixture was extracted with ethyl acetate (150 mL×3). The combined organic layers were washed with saturated aqueous sodium chloride (200 mL×2), dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=20/1 to give the title compound 1f as yellow oil (97 g, 43.5%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3) δ (ppm): 7.46 (m, 1H), 7.35 (m, 12H), 7.20 (m, 3H), 7.04 (m, 4H), 6.74 (m, 2H), 4.90 (m, 3H), 4.72 (d, 1H), 4.50 (d, 1H), 4.15 (t, 1H), 4.05 (d, 1H), 3.97 (m, 3H), 3.80 (m, 3H), 3.75 (m, 1H), 3.65 (m, 1H), 3.29 (d, 1H), 3.05 (s, 3H), 1.38 (t, 3H), 0.90 (s, 9H), 0.11 (s, 3H), 0.08 (s, 3H).

Workup

  1. temperatureto warm up to room temperature
  2. stirringthe mixture was stirred at 40° C. for 12 hours
  3. temperaturecooled to 0° C.
  4. customquenched with 50 mL of water
  5. customMost of the solvent was removed in vacuo
  6. additionTo the residue was added 200 mL of water
  7. extractionThe resulting mixture was extracted with ethyl acetate (150 mL×3)
  8. washThe combined organic layers were washed with saturated aqueous sodium chloride (200 mL×2)
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by silica gel chromatography
  12. washeluted with PE/EtOAc(v/v)=20/1

Sources & evidence

ORD record
ord-23ea1a31385b44c4955769c6ed7d11a1
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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