Isobutyryl chloride → [(1S)-1-[(3aR,5S,6aR)-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]propyl] 2-methylpropanoate

HRID 60771Notes

Reaction equation

HRID 60771 reaction equation
[CH3:1][C:2]1([CH3:14])[O:6][C@H:5]2[O:7][C@H:8]([C@@H:10]([OH:13])[CH2:11][CH3:12])[CH2:9][C@H:4]2[O:3]1.[C:15](Cl)(=[O:19])[CH:16]([CH3:18])[CH3:17]>N1C=CC=CC=1.CCOC(C)=O>[CH3:17][CH:16]([CH3:18])[C:15]([O:13][C@H:10]([C@H:8]1[O:7][C@@H:5]2[O:6][C:2]([CH3:1])([CH3:14])[O:3][C@@H:4]2[CH2:9]1)[CH2:11][CH3:12])=[O:19]

Participants

5

Reactant 2

HCID 62325Isobutyryl chlorideHCID 121396307(S)-1-((3AR,5S,6AR)-2,2-Dimethyltetrahydrofuro[2,3-D][1,3]dioxol-5-YL)propan-1-OL2×

Product 1

HCID 121396299[(1S)-1-[(3aR,5S,6aR)-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]propyl] 2-methylpropanoateYield 69%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a cooled solution of (1S)-1-[(3aR,5S,6aR)-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]propan-1-ol (compound 6e, 505.6 mg, 2.5 mmol) in pyridine was added isobutyryl chloride (0.39 mL, 3.72 mmol) dropwise while cooled with an ice-water bath. After the addition, the mixture was warmed to room temperature and stirred at room temperature overnight. The resulting mixture was diluted with EtOAc and washed with a saturated NH4Cl solution. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 0-30% EtOAc in petroleum ether) to afford 470 mg of [(1S)-1-[(3aR,5S,6aR)-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]propyl] 2-methylpropanoate (compound 42a).

Workup

  1. temperaturewhile cooled with an ice-water bath
  2. additionAfter the addition
  3. washwashed with a saturated NH4Cl solution
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography on silica gel (eluting with 0-30% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-ec34d855d7354e9cad168507bccf91be
Source dataset
uspto-grants-2016_09
Patent number
US09441008B2

Reaction notes

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