Dimethyl Sulfide → (S)-tert-butyl 1-(4-acetyl-2-fluorophenyl)ethylcarbamate

HRID 57434Notes

Reaction equation

HRID 57434 reaction equation
[C:1]([O:5][C:6](=[O:20])[NH:7][C@H:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16](C)=[CH2:17])=[CH:12][C:11]=1[F:19])[CH3:9])([CH3:4])([CH3:3])[CH3:2].C(Cl)Cl.CSC.CC[O:29]C(C)=O.CCCCCCC>O>[C:1]([O:5][C:6](=[O:20])[NH:7][C@H:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16](=[O:29])[CH3:17])=[CH:12][C:11]=1[F:19])[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 1068Dimethyl SulfideHCID 6344DichloromethaneHCID 21899848Ethylacetate heptaneHCID 131736958HCID 131736958, compound

Product 1

HCID 90417063(S)-tert-butyl 1-(4-acetyl-2-fluorophenyl)ethylcarbamateYield 23%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
-70 °C

Procedure

To a round bottom flask containing (S)-tert-butyl(1-(2-fluoro-4-(prop-1-en-2-yl)phenyl)ethyl)carbamate (1.28 g, 4.58 mmol) was added DCM (23 mL). The homogenous solution was cooled to −70° C. in a acetone/dry ice bath. Ozone (g) was then gently bubbled through the solution for 25 min at which time the solution becomes pale blue in color. Dimethyl sulfide (1.02 mL, 13.8 mmol) was then added to the cold solution and mixture gradually allowed to warm to room temperature and stirred for 30 min. Reaction mixture was diluted with a water. Phases partitioned. Aqueous phase extracted with DCM. Organic phases combined, washed with brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 0 to 60%) provided (S)-tert-butyl(1-(4-acetyl-2-fluorophenyl)ethyl)carbamate (296 mg, 1.05 mmol, 23% yield) as a colorless oil that crystallizes upon standing. 1H NMR (400 MHz, CDCl3) δ 1.38-1.49 (m, 12H) 2.59 (s, 3H) 5.01 (br. s., 1H) 7.40 (t, J=7.65 Hz, 1H) 7.62 (dd, J=11.20, 1.57 Hz, 1H) 7.71 (dd, J=7.95, 1.54 Hz, 1H). LCMS m/z 267.1 (carboxylic acid fragment+CH3CN) (M+H)+, Rt 0.89 min.

Workup

  1. customOzone (g) was then gently bubbled through the solution for 25 min at which time the solution
  2. temperatureto warm to room temperature
  3. customReaction mixture
  4. customPhases partitioned
  5. extractionAqueous phase extracted with DCM
  6. washwashed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated onto silica gel

Sources & evidence

ORD record
ord-57da3569391e44a5aba435823e2cb66e
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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