Sodium hydride → HCID 117974467, compound

HRID 1776088Notes

Reaction equation

HRID 1776088 reaction equation
[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([CH2:7][O:8][C@H:9]([C@H:11]([OH:20])[C@H:12]([CH:18]=[CH2:19])[CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[CH3:10])=[CH:5][CH:4]=1.[H-].[Na+].Br[CH2:26][CH:27]1[CH2:29][CH2:28]1>CN(C=O)C>[CH:27]1([CH2:26][O:20][C@H:11]([C@H:12]([CH:18]=[CH2:19])[CH2:13][CH2:14][CH:15]([CH3:16])[CH3:17])[C@@H:9]([O:8][CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:22][CH:21]=2)[CH3:10])[CH2:29][CH2:28]1

Participants

5

Reactant 3

HCID 24758Sodium hydride3×HCID 81503Bromomethylcyclopropane3×HCID 117974371HCID 117974371, compound

Product 1

HCID 117974467HCID 117974467, compoundYield 82.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of (2S,3R,4S)-2-((4-methoxybenzyl)oxy)-7-methyl-4-vinyloctan-3-ol (2.0 g, 6.53 mmol) in anhydrous DMF (12 mL) was added at room temperature to a solution of NaH (NaH; 0.326 g, 8.16 mmol, 60% dispersion in mineral oil) in anhydrous DMF (12 ml). The reaction was stirred for 15 minutes (min) at room temperature, treated with (bromomethyl)cyclopropane (0.823 ml, 8.48 mmol) at room temperature, and then was heated to 40° C. for and stirred for 6 h. The reaction was cooled to room temperature and additional NaH (0.131 g, 3.27 mmol) and (bromomethyl)cyclopropane (0.317 mL, 3.27 mmol) were added, and the reaction was heated at 45° C. for 4 h. The reaction was again cooled to room temperature and a third batch of NaH (0.131 g, 3.27 mmol) followed by (bromomethyl)cyclopropane (0.317 mL, 3.27 mmol) was added and the reaction was heated at 45° C. for 2 h. The reaction mixture was quenched with saturated aqueous ammonium chloride (NH4Cl) and the phases were separated. The aqueous phase was extracted with diethyl ether (Et2O), and the combined organic phases were washed with brine, dried over magnesium sulfate (MgSO4), concentrated, and purified by column chromatography on SiO2 (gradient, hexanes/ethyl acetate) to furnish the title product as a colorless oil (1.94 g, 82%): IR (neat) 2953, 2868, 1613, 1513, 1247, 1084 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.25-7.20 (m, 2H), 6.89-6.81 (m, 2H), 5.52 (dt, J=17.0, 10.0 Hz, 1H), 5.03-4.92 (m, 2H), 4.52-4.32 (m, 2H), 3.78 (s, 3H), 3.65-3.56 (m, 2H), 3.34 (dd, J=10.0, 6.9 Hz, 1H), 3.28-3.22 (m, 1H), 2.09 (tdd, J=10.1, 7.7, 3.1 Hz, 1H), 1.81-1.67 (m, 1H), 1.55-1.42 (m, 1H), 1.28-1.13 (m, 2H), 1.19 (d, J=6.3 Hz, 3H), 1.13-0.95 (m, 2H), 0.87 (d, J=6.4 Hz, 3H), 0.86 (d, J=6.8 Hz, 3H), 0.56-0.45 (m, 2H), 0.25-0.14 (m, 2H); ESIMS m/z 383.4 ([M+Na]+).

Workup

  1. temperaturewas heated to 40° C. for and
  2. stirringstirred for 6 h
  3. temperatureThe reaction was cooled to room temperature
  4. temperaturethe reaction was heated at 45° C. for 4 h
  5. temperatureThe reaction was again cooled to room temperature
  6. additionwas added
  7. temperaturethe reaction was heated at 45° C. for 2 h
  8. customThe reaction mixture was quenched with saturated aqueous ammonium chloride (NH4Cl)
  9. customthe phases were separated
  10. extractionThe aqueous phase was extracted with diethyl ether (Et2O)
  11. washthe combined organic phases were washed with brine
  12. dry with materialdried over magnesium sulfate (MgSO4)
  13. concentrationconcentrated
  14. custompurified by column chromatography on SiO2 (gradient, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-2d5719ced59a40e7ac9eea753a07702a
Source dataset
uspto-grants-2016_02
Patent number
US09265253B2

Reaction notes

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