2-Methoxypropene → (S)-4-(2-Hydroxy-ethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid benzyl ester

HRID 655546Notes

Reaction equation

HRID 655546 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:15][CH2:16][OH:17])[CH2:13][OH:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO[C:20]([CH3:22])=[CH2:21]>COC(OC)(C)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:1]([O:8][C:9]([N:11]1[C@@H:12]([CH2:15][CH2:16][OH:17])[CH2:13][O:14][C:20]1([CH3:22])[CH3:21])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 83002-MethoxypropeneHCID 7022411(S)-2-Cbz-aminobutane-1,4-diol

Product 1

HCID 60098506(S)-4-(2-Hydroxy-ethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid benzyl esterYield 96%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 64952,2-DimethoxypropaneSolvent

Procedure

A solution of (S)—N-(benzyloxycarbonyl)-2-aminobutane-1,4-diol (8.00 g, 33.4 mmol) and toluene-4-sulfonic acid monohydrate (318 mg, 1.67 mmol) in 2,2-dimethoxypropane (320 mL) was stirred at room temperature, then after 2 h 2-methoxypropene (7.71 g, 107 mmol) was added, then after 72 h the reaction mixture was partitioned between ethyl acetate and sat. aq. sodium hydrogencarbonate solution. The organic layer was dried (MgSO4), filtered, and evaporated. The residue was taken up in dichloromethane (200 mL), then after addition of SiO2 (80 g) and water (4.8 mL) the slurry was stirred for 64 h at room temperature. After dilution with dichloromethane and addition of anhydrous magnesium sulfate, insoluble material was removed by filtration through diatomaceous earth. The filtrate was evaporated and chromatographed (SiO2; heptane/ethyl acetate 1:1) to afford the title compound (8.92 g, 96%). Light yellow oil, MS (ISP)=280.1 (M+H)+.

Workup

  1. customafter 72 h the reaction mixture was partitioned between ethyl acetate and sat. aq. sodium hydrogencarbonate solution
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. additionafter addition of SiO2 (80 g) and water (4.8 mL) the slurry
  6. additionAfter dilution with dichloromethane and addition of anhydrous magnesium sulfate, insoluble material
  7. customwas removed by filtration through diatomaceous earth
  8. customThe filtrate was evaporated
  9. customchromatographed (SiO2; heptane/ethyl acetate 1:1)

Sources & evidence

ORD record
ord-566f1c7583c7486f9f3e773a2008d3ff
Source dataset
uspto-grants-2011_12
Patent number
US08071586B2

Reaction notes

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