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

HRID 1261834Notes

Reaction equation

HRID 1261834 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 EtOAc and sat. aq. sodium hydrogencarbonate solution. The organic layer was dried over magnesium sulfate, filtered, and evaporated. The residue was taken up in DCM (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 DCM and addition of anhydrous magnesium sulfate, insoluble material was removed by filtration through diatomaceous earth. The filtrate was evaporated and chromatographed (SiO2; heptane/EtOAc 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 EtOAc and sat. aq. sodium hydrogencarbonate solution
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. additionafter addition of SiO2 (80 g) and water (4.8 mL) the slurry
  6. additionAfter dilution with DCM 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/EtOAc 1:1)

Sources & evidence

ORD record
ord-ff0024e2a0d649d5bffcdcbb39e91406
Source dataset
uspto-grants-2013_06
Patent number
US08471004B2

Reaction notes

Loading…