Hydrochloric Acid → tert-Butyl 3-(2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-5-fluorophenyl)-3-oxopropyl(methyl)carbamate

HRID 426060Notes

Reaction equation

HRID 426060 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[O:10][CH2:11][C:12]([CH3:15])([CH3:14])[N:13]=1.CON(C)[C:19](=[O:31])[CH2:20][CH2:21][N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26].Cl>C1COCC1.CCCCC>[CH3:14][C:12]1([CH3:15])[CH2:11][O:10][C:9]([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[C:19](=[O:31])[CH2:20][CH2:21][N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[N:13]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 59364357Tert-butyl 3-(methoxy(methyl)amino)-3-oxopropyl(methyl)carbamateHCID 593643802-(2-Bromo-4-fluorophenyl)-4,4-dimethyl-4,5-dihydrooxazole

Product 1

HCID 59364358tert-Butyl 3-(2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-5-fluorophenyl)-3-oxopropyl(methyl)carbamateYield 61.4%

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

A stirred solution of 2-(2-bromo-4-fluorophenyl)-4,4-dimethyl-4,5-dihydrooxazole (1.2 g, 4.7 mmol) in dry THF (6 mL) was cooled to −78° C. and a solution of tert-buLi (1.7 M in pentane, 5.5 mL, 9.3 mmol) was added drop wise. After 30 min, a solution of tert-butyl 3-(methoxy(methyl)amino)-3-oxopropyl(methyl)carbamate (0.77 g, 3.1 mmol) in dry THF (5 mL) was added. The cooling bath was allowed to warm to −20° C. and the reaction mixture was stirred between −20° C. and 0° C. for 4 h. After warming to room temperature, the mixture was added 0.2N HCl (50 mL). The mixture was extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (120 g column, 0% ethyl acetate in hexanes to 60% ethyl acetate in hexanes) to give product (0.72 g, 61%). 1H NMR (CDCl3) 7.62 (brs, 1H), 6.88 (t, J=7.5 Hz, 1H), 6.79 (brs, 1H), 3.80-4.00 (m, 2H), 3.30 (t, J=7.0 Hz, 2H), 2.76 (brs, 2H), 2.59 (s, 3H), 1.13 (s, 15H); MS EI m/z 379 (M+H)+.

Workup

  1. temperatureAfter warming to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (2×100 mL)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (120 g column, 0% ethyl acetate in hexanes to 60% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-4d2cd70ae6eb4478ac05fca53901df45
Source dataset
uspto-grants-2012_01
Patent number
US08106221B2

Reaction notes

Loading…