(S)-tert-butyl 1-(4-acetyl-2-fluorophenyl)ethylcarbamate → HCID 131736959, compound

HRID 57435Notes

Reaction equation

HRID 57435 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](=[O:18])[CH3:17])=[CH:12][C:11]=1[F:19])[CH3:9])([CH3:4])([CH3:3])[CH3:2].[CH3:21][Mg+].[Br-]>C(Cl)Cl.C(OCC)C>[C:1]([O:5][C:6](=[O:20])[NH:7][C@H:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16]([OH:18])([CH3:21])[CH3:17])=[CH:12][C:11]=1[F:19])[CH3:9])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 2

HCID 90417063(S)-tert-butyl 1-(4-acetyl-2-fluorophenyl)ethylcarbamateHCID 178418689HCID 178418689, compound

Product 1

HCID 131736959HCID 131736959, compoundYield 92.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-tert-butyl(1-(4-acetyl-2-fluorophenyl)ethyl)carbamate (296 mg, 1.05 mmol) in DCM (5.2 mL), cooled to 0° C. (water/ice bath) under N2, was added 3M MeMgBr (1.4 mL, 4.21 mmol) in diethyl ether. Reaction mixture allowed to stir for 5 min at 0° C. Then gradually allowed to warm to room temperature and stirred for 30 min at room temperature. Reaction mixture was cooled to 0° C. then quenched with the slow addition of a saturated solution of NH4Cl and diluted with DCM. Phases partitioned, aqueous phase extracted with DCM and the organic layers combined washed with water, brine, dried (Na2SO4), filtered and concentrated to (S)-tert-butyl(1-(2-fluoro-4-(2-hydroxypropan-2-yl)phenyl)ethyl)carbamate (288 mg, 0.97 mmol, 92% yield) afford as a colorless oil which slowly crystallizes upon standing. 1H NMR (400 MHz, CDCl3) δ 1.39-1.48 (m, 12H) 1.57 (s, 6H) 7.15-7.25 (m, 2H) 7.31-7.36 (m, 1H).

Workup

  1. customReaction mixture
  2. temperatureto warm to room temperature
  3. stirringstirred for 30 min at room temperature
  4. customReaction mixture
  5. temperaturewas cooled to 0° C.
  6. customthen quenched with the slow addition of a saturated solution of NH4Cl
  7. additiondiluted with DCM
  8. customPhases partitioned
  9. extractionaqueous phase extracted with DCM
  10. washthe organic layers combined washed with water, brine
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered

Sources & evidence

ORD record
ord-e5d474371e654716a8384f1b82f1cc07
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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