Dichloromethane → Methyl 2-(benzyloxycarbonyl)acrylate

HRID 2099810Notes

Reaction equation

HRID 2099810 reaction equation
[CH2:1]([O:8][C:9]([CH:11]([CH2:16]O)[C:12]([O:14][CH3:15])=[O:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)Cl.CS(Cl)(=O)=O>C(N(CC)CC)C>[CH2:1]([O:8][C:9]([C:11](=[CH2:16])[C:12]([O:14][CH3:15])=[O:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 31297Methanesulfonyl chlorideHCID 66604350Methyl 2-(benzyloxycarbonyl)-3-hydroxypropanoate

Product 1

HCID 66604662Methyl 2-(benzyloxycarbonyl)acrylateYield 92%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent3×

Conditions

Temperature
20 °C

Procedure

To a flame dried three neck round bottom flask, was added methyl 2-(benzyloxycarbonyl)-3-hydroxypropanoate (129 g, 509 mmol), anhydrous methylene chloride (2 L), and methanesulfonyl chloride (49.3 mL, 636 mmol). The mixture was cooled to −15° C.→20° C. for 20 min while stirring with a mechanical stirrer. Triethylamine (213 mL, 1527 mmol) was added dropwise ensuring the inner temperature of the reaction mixture did not exceed 0° C. (the addition of the first equivalent of triethylamine was exothermic). After the addition of triethylamine, the mixture was stirred at 0° C. for 30 min, then the cooling bath was removed and the mixture was stirred at room temperature for 1.5 h. Methanol (21 mL) was added to quench excess methanesulfonyl chloride. The mixture was washed portionwise with 0.5% aq. potassium hydrogen sulfate to pH 5, then sat. sodium bicarbonate/brine (1:2 by volume) and brine. The methylene chloride solution was dried over anhydrous sodium sulfate. After filtration, the solvents were removed and the residue was subjected to column chromatography on silica gel using 1:9 ethyl acetate/hexanes as eluent to afford the title compound as a colorless very viscous oil, which recrystalized upon standing at room temperature, 0° C. and −15° C. (111 g, 92% yield). 1H-NMR (DMSO-d6) δ 8.96 (s, 1H), 7.39-7.35 (m, 5H), 5.76 (s, 1H), 5.60 (s, 1H), 5.10 (s, 2H), 3.71 (s, 3H); 13C-NMR (DMSO-d6) δ 163.7, 153.5, 136.3, 133.3, 128.8, 128.3, 128.1, 127.8, 65.9, 52.3.

Workup

  1. customTo a flame dried three neck round bottom flask
  2. customdid not exceed 0° C.
  3. stirringthe mixture was stirred at 0° C. for 30 min
  4. customthe cooling bath was removed
  5. stirringthe mixture was stirred at room temperature for 1.5 h
  6. additionMethanol (21 mL) was added
  7. customto quench excess methanesulfonyl chloride
  8. washThe mixture was washed portionwise with 0.5% aq. potassium hydrogen sulfate to pH 5
  9. dry with materialThe methylene chloride solution was dried over anhydrous sodium sulfate
  10. filtrationAfter filtration
  11. customthe solvents were removed

Sources & evidence

ORD record
ord-1de7c06df2314d4d85c3a6cdb9c39174
Source dataset
uspto-grants-2009_08
Patent number
US07569578B2

Reaction notes

Loading…