Methanol → HCID 60023926, compound

HRID 1782180Notes

Reaction equation

HRID 1782180 reaction equation
[CH:1]([Mg]Br)=[CH2:2].CON(C)[C:8](=[O:21])[C@H:9]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH:10]([CH3:12])[CH3:11].C(OC(=O)C)(=O)C.CO>O1CCCC1>[CH3:12][CH:10]([C@@H:9]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19])[C:8](=[O:21])[CH:1]=[CH2:2])[CH3:11]

Participants

6

Reactant 4

HCID 887MethanolHCID 7918Acetic AnhydrideHCID 54281446N~2~-(tert-Butoxycarbonyl)-N-methoxy-N-methyl-D-valinamideHCID 178418507HCID 178418507, compound

Product 1

HCID 60023926HCID 60023926, compoundYield 64.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Vinylmagnesium bromide (1M soln in THF, 34.6 mL, 34.6 mmol) was added to a solution of (R)-tert-butyl 1-(methoxy(methyl)amino)-3-methyl-1-oxobutan-2-ylcarbamate (4.5 g, 17.30 mmol) in anhydrous tetrahydrofuran (50 mL) under nitrogen at −78° C., dropwise, over 20 min. The reaction was slowly warmed to 0° C. and then stirred for an hour at 0° C. The reaction warmed to room temperature and then stirred for 10 h. Acetic anhydride (10 mL) was added to the reaction mixture at 0° C. After several minutes methanol (10 mL) was added to the reaction. The mixture was allowed to stir for 10 min, and then concentrated to a volume of 25 mL. The reaction mixture was washed with water (100 mL) and the aqueous layer was extracted with ethyl acetate (150 mL). The combined organic layers were washed successively with aqueous sodium bicarbonate (2×100 mL) and brine (2×100 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure at less than 40° C. The resulting residue was purified by flash column chromatography on silica gel, eluting with 85:15 hexanes:ethyl acetate to provide (R)-tert-butyl 2-methyl-4-oxohex-5-en-3-ylcarbamate (2.52 g) as a white solid. 1H NMR (CDCl3): 6.50-6.32 (m, 2H), 5.85 (d, 1H), 5.22 (d, 1H), 4.56 (dd, 1H), 2.18 (m, 1H), 1.44 (s, 9H), 1.01 (d, 3H), 0.80 ppm (d, 3H).

Workup

  1. temperatureThe reaction warmed to room temperature
  2. stirringstirred for 10 h
  3. stirringto stir for 10 min
  4. concentrationconcentrated to a volume of 25 mL
  5. washThe reaction mixture was washed with water (100 mL)
  6. extractionthe aqueous layer was extracted with ethyl acetate (150 mL)
  7. washThe combined organic layers were washed successively with aqueous sodium bicarbonate (2×100 mL) and brine (2×100 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure at less than 40° C
  11. customThe resulting residue was purified by flash column chromatography on silica gel
  12. washeluting with 85:15 hexanes

Sources & evidence

ORD record
ord-f103eeb2d91449ebbbaf3a89ad18b677
Source dataset
uspto-grants-2009_03
Patent number
US07498353B2

Reaction notes

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