Dichloromethane methanol → HCID 67349681, compound

HRID 722725Notes

Reaction equation

HRID 722725 reaction equation
[CH3:1][O:2][C:3](=[O:18])[CH:4]([NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:5][O:6][CH2:7][CH:8]=C.C(Cl)Cl.[CH3:22][OH:23]>>[CH3:1][O:2][C:3]([CH:4]1[CH2:5][O:6][CH2:7][CH:8]([O:23][CH3:22])[N:10]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:18]

Participants

3

Reactant 2

HCID 21226129Dichloromethane methanolHCID 53364070HCID 53364070, compound

Product 1

HCID 67349681HCID 67349681, compoundYield 78%

Conditions

Temperature
-78 °C

Procedure

A solution containing 3-allyloxy-2-tert-butoxycarbonylamino-propionic acid methyl ester (30.0 g, 116 mmol) in 550 mL of 10:1 CH2Cl2/MeOH is cooled to −78° C. and purged with ozone until a blue color persisted (45 min). The solution is then purged with N2 to remove excess ozone and treated with dimethylsulfide (35 mL). The solution is allowed to warm to room temperature overnight and the next morning concentrated in vacuo. The resulting solid is re-dissolved in 400 mL of MeOH and treated with 500 mg of p-toluenesulfonic acid. After stirring for 4 hours, the volume of solvent is reduced to about 100 mL and toluene (250 mL) is added. The solution is re-concentrate in vacuo and purified over silica gel (EtOAc/hexane) to afford 25 g (78%) of the desired product. 1H NMR (CDCl3) δ 5.21 (br s, 0.5H), 5.05 (br s, 0.5H), 4.65–4.45 (m, 2H), 3.98 (dd, J=12.8, 12.5 Hz, 1H), 3.79 (s, 3H), 3.66 (br d, J=11.3 Hz, 1H), 3.56 (dd, J=9.9, 9.9 Hz, 1H), 3.42 (s, 3H), 1.54 (s, 0.5×9H), 1.50 (s, 0.5×9H); MS 276 (M+H)+.

Workup

  1. custompurged with ozone until a blue color
  2. custom(45 min)
  3. customThe solution is then purged with N2
  4. customto remove excess ozone
  5. additiontreated with dimethylsulfide (35 mL)
  6. temperatureto warm to room temperature overnight
  7. concentrationthe next morning concentrated in vacuo
  8. dissolutionThe resulting solid is re-dissolved in 400 mL of MeOH
  9. additiontreated with 500 mg of p-toluenesulfonic acid
  10. additionis added
  11. concentrationThe solution is re-concentrate in vacuo
  12. custompurified over silica gel (EtOAc/hexane)

Sources & evidence

ORD record
ord-8b211572b87041fb83ff710330ac321b
Source dataset
uspto-grants-2006_11
Patent number
US07138395B2

Reaction notes

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