3-Bromo-5-fluorobenzotrifluoride → benzyl {(2S)-1-[3-fluoro-5-(trifluoromethyl)phenyl]-1-oxopropan-2-yl}carbamate

HRID 1508589Notes

Reaction equation

HRID 1508589 reaction equation
CON(C)[C:4](=[O:18])[C@@H:5]([NH:7][C:8](=[O:17])[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:6].Br[C:21]1[CH:22]=[C:23]([C:28]([F:31])([F:30])[F:29])[CH:24]=[C:25]([F:27])[CH:26]=1.C([Mg]Cl)(C)C>C1COCC1.[Cl-].[Na+].O>[F:27][C:25]1[CH:26]=[C:21]([C:4](=[O:18])[C@@H:5]([NH:7][C:8](=[O:17])[O:9][CH2:10][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH3:6])[CH:22]=[C:23]([C:28]([F:29])([F:30])[F:31])[CH:24]=1

Participants

6

Reactant 3

HCID 27363233-Bromo-5-fluorobenzotrifluorideHCID 10515879(S)-Benzyl 1-(methoxy(methyl)amino)-1-oxopropan-2-ylcarbamateHCID 178418918HCID 178418918, compound

Product 1

HCID 86704637benzyl {(2S)-1-[3-fluoro-5-(trifluoromethyl)phenyl]-1-oxopropan-2-yl}carbamate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of the commercially available benzyl {(2S)-1-[methoxy(methyl)amino]-1-oxopropan-2-yl}carbamate (5.48 g, 20.58 mmol) and 3-bromo-5-fluorobenzotrifluoride (5 g, 20.58 mmol) in THF (52 ml) at −30° C. was added isopropylmagnesium chloride (20.58 ml, 41.2 mmol) dropwise under nitrogen. Removed the cold bath and allowed the reaction to age overnight to ambient temperature. The crude was cooled to −20° C. followed by addition of HC (1N, ice bath cold). The resulting mixture was worked up with brine, extracted with ethyl acetate, dried over Na2SO4, filtered and evaporated. The pot residue was purified by flash chromatography (SiO2, Biotage 65i cartridge). The column was eluted by an ethyl acetate/hexanes mixture (0% to 40% ethyl acetate). Related fractions were pooled and evaporated under reduced pressure to afford a yellow oil of 5.4655 g as the titled compound. 1H-NMR (CDCl3, 500 MHz) δ 8.03 (s, 1H), 7.86 (d, J=8.5 Hz, 1H), 7.57 (d, J=8 Hz, 1H), 7.38-7.30 (m, 5H), 5.7 (d, J=7.5 Hz, 1H), 5.3 (ps quintet, J=7.5 Hz, 1H), 1.45 (d, J=7 Hz, 3H).

Workup

  1. customRemoved the cold bath
  2. customthe reaction to age overnight to ambient temperature
  3. additionfollowed by addition of HC (1N, ice bath cold)
  4. extractionextracted with ethyl acetate
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe pot residue was purified by flash chromatography (SiO2, Biotage 65i cartridge)
  9. washThe column was eluted by an ethyl acetate/hexanes mixture (0% to 40% ethyl acetate)
  10. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-1492c68e01c24dbeaf291884ebd83c24
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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