Benzyl Bromide → HCID 117974159, compound

HRID 1776090Notes

Reaction equation

HRID 1776090 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:5]=1[CH2:6][C@@H:7]([CH:22]=[CH2:23])[C@@H:8]([OH:21])[C@@H:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1)[CH3:10].[CH2:29](Br)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>CN(C=O)C>[CH2:29]([O:21][C@@H:8]([C@@H:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1)[CH3:10])[C@H:7]([CH:22]=[CH2:23])[CH2:6][C:5]1[CH:24]=[CH:25][C:26]([F:28])=[CH:27][C:4]=1[F:3])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 117974453HCID 117974453, compound

Product 1

HCID 117974159HCID 117974159, compoundYield 84.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

An oven-dried 100 mL Schlenk flask was cooled under nitrogen and was then charged with NaH (60% dispersion in mineral oil, 1.24 g, 31.0 mmol) and anhydrous DMF (50 mL). A solution of (2S,3R,4S)-4-(2,4-difluorobenzyl)-2-((4-methoxybenzyl)oxy)hex-5-en-3-ol (8.06 g, 22.2 mmol) in anhydrous DMF (10 mL) was added via canula over a period of 6 min followed by an anhydrous DMF rinse (5 mL) of the source flask and needle. Gas evolution was observed, and the resulting white suspension was stirred at room temperature for 90 min, at which point the reaction color had turned red. Benzyl bromide (4.23 mL, 35.6 mmol) was added and the reaction was heated to 40° C. After stirring for 3 hours, the heat source was removed and the reaction was cooled to room temperature. Saturated aqueous NH4Cl solution (20 mL) was added, and the mixture was allowed to stir for 30 min, at which point gas evolution had ceased. The crude mixture was then diluted with H2O (50 mL) and extracted with Et2O (100 mL×3). The combined organic extracts were washed with saturated aqueous NH4Cl solution (100 mL), dried over anhydrous MgSO4, filtered, concentrated, and the residue was purified by column chromatography on SiO2 (0%→10% methyl tert-butylether (MTBE)/hexane gradient) to furnish the title product as white solid (90% Pure, 8.47 g, 84%): mp 141-144° C.; 1H NMR (400 MHz, CDCl3) δ 7.41-7.30 (m, 4H), 7.30-7.24 (m, 3H), 7.05-6.96 (m, 1H), 6.90-6.84 (m, 2H), 6.76-6.67 (m, 2H), 5.57 (dddd, J=17.1, 10.3, 9.0, 1.3 Hz, 1H), 4.88 (dd, J=10.2, 1.9 Hz, 1H), 4.87 (d, J=11.4 Hz, 1H), 4.72 (ddd, J=17.2, 1.8, 0.5 Hz, 1H), 4.63 (d, J=11.4 Hz, 1H), 4.53 (d, J=11.3 Hz, 1H), 4.40 (d, J=11.3 Hz, 1H), 3.79 (s, 3H), 3.70 (qd, J=6.2, 3.8 Hz, 1H), 3.52 (dd, J=6.9, 3.9 Hz, 1H), 3.09 (d, J=10.4 Hz, 1H), 2.59-2.44 (m, 2H), 1.25 (d, J=6.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 161.24 (dd, J=245.7, 11.9 Hz), 161.09 (dd, J=247.0, 11.6 Hz), 159.11, 138.90, 138.24, 132.05 (dd, J=9.4, 6.7 Hz), 130.92, 129.17, 128.33, 127.97, 127.53, 123.45 (dd, J=15.9, 3.7 Hz), 116.95, 113.78, 110.59 (dd, J=20.8, 3.7 Hz), 103.33 (dd, J=26.5, 25.0 Hz), 83.67, 76.56, 74.18, 70.41, 55.28, 47.98, 29.75, 14.24; 19F NMR (376 MHz, CDCl3) δ −113.06 (d, J=6.8 Hz), −113.95 (d, J=6.4 Hz); ESIMS: m/z 475 ([M+Na]+).

Workup

  1. temperatureAn oven-dried 100 mL Schlenk flask was cooled under nitrogen
  2. washrinse (5 mL) of the source flask and needle
  3. temperaturethe reaction was heated to 40° C
  4. stirringAfter stirring for 3 hours
  5. customthe heat source was removed
  6. temperaturethe reaction was cooled to room temperature
  7. additionSaturated aqueous NH4Cl solution (20 mL) was added
  8. stirringto stir for 30 min, at which point gas evolution
  9. additionThe crude mixture was then diluted with H2O (50 mL)
  10. extractionextracted with Et2O (100 mL×3)
  11. washThe combined organic extracts were washed with saturated aqueous NH4Cl solution (100 mL)
  12. dry with materialdried over anhydrous MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customthe residue was purified by column chromatography on SiO2 (0%→10% methyl tert-butylether (MTBE)/hexane gradient)

Sources & evidence

ORD record
ord-e53af50c1bfb4692902a5d5392f3aa89
Source dataset
uspto-grants-2016_02
Patent number
US09265253B2

Reaction notes

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