Dimethylformamide → (4S,5S)-tert-butyl 4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-5-(hydroxymethyl)-2,2-dimethyloxazolidine-3-carboxylate

HRID 1697192Notes

Reaction equation

HRID 1697192 reaction equation
C(OC[C@@H](O)[C@@H:7]([C:20]([O:22][C:23]([CH3:26])([CH3:25])C)=O)[CH2:8][C:9]1[CH:19]=[CH:18][C:12]2[O:13][C:14]([F:17])([F:16])[O:15][C:11]=2[CH:10]=1)(=O)C.[CH3:28][O:29]C(C)=C.CC1(C)[C:38]2(CS(O)(=O)=O)[C:39]([CH2:41]C1CC2)=[O:40].[C:48](=O)([O-])[O-].[K+].[K+].C[N:55]([CH:57]=[O:58])C>C(OCC)(=O)C.[Cl-].[NH4+]>[F:17][C:14]1([F:16])[O:13][C:12]2[CH:18]=[CH:19][C:9]([CH2:8][C@H:7]3[C@@H:20]([CH2:28][OH:29])[O:22][C:23]([CH3:25])([CH3:26])[N:55]3[C:57]([O:40][C:39]([CH3:41])([CH3:48])[CH3:38])=[O:58])=[CH:10][C:11]=2[O:15]1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 83002-Methoxypropene2×HCID 11430Potassium CarbonateHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-2×HCID 67164512(2S,3S)-3-(tert-butoxycarbonyl)-4-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-2-hydroxybutyl acetate

Product 1

HCID 67163920(4S,5S)-tert-butyl 4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-5-(hydroxymethyl)-2,2-dimethyloxazolidine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of (2S,3S)-3-(tert-butoxycarbonyl)-4-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-2-hydroxybutyl acetate (1050 mg, 2603 μmol) in 5 mL of DMF was added 2-methoxypropene (872 μl, 9111 μmol) and CSA (181 mg, 781 μmol). The mixture was stirred at rt overnight, and 91 mg of CSA and 0.872 mL of 2-methoxypropene were added. The reaction was stirred for 2 hours, then poured into ice-cold aqueous saturated sodium bicarbonate (150 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water, brine, and dried over sodium sulfate. The derived yellow oil was taken up in 10 mL of methanol cooled to 0° C. and treated with potassium carbonate (1079 mg, 7809 μmol). After warming to rt over the course of 1 hour the reaction was diluted with ethyl acetate (25 mL) and poured in saturated ammonium chloride (50 mL). The aqueous layer was extracted with ethyl acetate (3×50 mL) and the combined organic layers were washed with water and then brine and dried over Na2SO4. Concentration of the solvents under reduced pressure and purification by silica gel provided (4S,5S)-tert-butyl 4-((2,2-difluorobenzo[d][1,3]dioxol-5-yl)methyl)-5-(hydroxymethyl)-2,2-dimethyloxazolidine-3-carboxylate as a colorless oil.

Workup

  1. stirringThe reaction was stirred for 2 hours
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. washThe combined organic layers were washed with water, brine
  4. dry with materialdried over sodium sulfate
  5. temperaturecooled to 0° C.
  6. temperatureAfter warming to rt over the course of 1 hour the reaction
  7. extractionThe aqueous layer was extracted with ethyl acetate (3×50 mL)
  8. washthe combined organic layers were washed with water
  9. dry with materialbrine and dried over Na2SO4
  10. customConcentration of the solvents under reduced pressure and purification by silica gel

Sources & evidence

ORD record
ord-a546cca0ed8e44c79e68f3c97482b73d
Source dataset
uspto-grants-2012_04
Patent number
US08163909B2

Reaction notes

Loading…