Sodium hydride → HCID 117974494, compound

HRID 1776089Notes

Reaction equation

HRID 1776089 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+].[CH3:25][C:26]1[CH:31]=CC(S(OCC(C)C)(=O)=O)=C[CH:27]=1>CN(C=O)C>[CH2:25]([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]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:22][CH:21]=1)[CH3:10])[CH:26]([CH3:31])[CH3:27]

Participants

5

Reactant 3

HCID 24758Sodium hydride3×HCID 3105902-Methylpropyl 4-methylbenzene-1-sulfonate3×HCID 117974371HCID 117974371, compound

Product 1

HCID 117974494HCID 117974494, compoundYield 87%

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 (15 mL) was added at room temperature to a solution of NaH (0.326 g, 8.16 mmol, 60% dispersion in mineral oil) in anhydrous DMF (6.0 mL). The reaction was stirred for 15 min at room temperature, then isobutyl 4-methylbenzenesulfonate (1.66 mL, 8.16 mmol) was added at room temperature and the reaction was heated at 50° C. and stirred for 1 h. The reaction was cooled down to room temperature and NaH (0.261 g, 6.53 mmol) followed by isobutyl 4-methylbenzenesulfonate (1.33 mL, 6.53 mmol) were added and heating continued for 2 h at 50° C., after which the reaction was again cooled down to room temperature and a third batch of NaH (0.131 g, 3.27 mmol) and isobutyl 4-methylbenzenesulfonate (0.67 mL, 3.27 mmol) were added and the reaction was heated at 50° C. for 7 h. The reaction mixture was quenched with saturated NH4Cl and the phases were separated. The aqueous phase was extracted with Et2O, and the combined organic phases were washed with brine, dried over MgSO4, concentrated, and purified by column chromatography on SiO2 (gradient, hexanes/ethyl acetate) to furnish the title product as a colorless oil (2.05 g, 87%): 1H NMR (400 MHz, CDCl3) δ 7.29-7.21 (m, 2H), 6.90-6.83 (m, 2H), 5.61-5.49 (m, 1H), 5.04-4.89 (m, 2H), 4.53-4.33 (m, 2H), 3.80 (s, 3H), 3.64-3.51 (m, 2H), 3.28-3.16 (m, 2H), 2.15-2.02 (m, 1H), 1.90-1.77 (m, 1H), 1.76-1.60 (m, 1H), 1.54-1.41 (m, 1H), 1.28-1.11 (m, 2H), 1.17 (d, J=6.3 Hz, 3H), 1.08-0.96 (m, 1H), 0.95-0.88 (m, 6H), 0.86 (d, J=6.4 Hz, 3H), 0.85 (d, J=6.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 158.97, 140.43, 131.09, 129.06, 115.66, 113.67, 84.26, 79.58, 76.41, 70.05, 55.26, 47.38, 36.46, 29.13, 28.21, 27.85, 22.91, 22.47, 19.66, 19.55, 14.25; ESIMS m/z 385.4 ([M+Na]+).

Workup

  1. temperaturethe reaction was heated at 50° C.
  2. stirringstirred for 1 h
  3. temperatureThe reaction was cooled down to room temperature
  4. additionwere added
  5. temperatureheating
  6. waitcontinued for 2 h at 50° C.
  7. temperatureafter which the reaction was again cooled down to room temperature
  8. temperaturethe reaction was heated at 50° C. for 7 h
  9. customThe reaction mixture was quenched with saturated NH4Cl
  10. customthe phases were separated
  11. extractionThe aqueous phase was extracted with Et2O
  12. washthe combined organic phases were washed with brine
  13. dry with materialdried over MgSO4
  14. concentrationconcentrated
  15. custompurified by column chromatography on SiO2 (gradient, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-12eb8bee3f16417aa73771f795dc963a
Source dataset
uspto-grants-2016_02
Patent number
US09265253B2

Reaction notes

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