1-Bromo-3-(trifluoromethoxy)benzene → HCID 86704636, compound

HRID 1508587Notes

Reaction equation

HRID 1508587 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:26]=[CH:25][CH:24]=[C:23]([O:27][C:28]([F:31])([F:30])[F:29])[CH:22]=1.C([Mg]Cl)(C)C>C1COCC1>[O:18]=[CH:4][C@@H:5]([NH:7][C:8](=[O:17])[O:9][CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[CH2:6][C:25]1[CH:26]=[CH:21][CH:22]=[C:23]([O:27][C:28]([F:29])([F:30])[F:31])[CH:24]=1

Participants

5

Reactant 3

HCID 5199641-Bromo-3-(trifluoromethoxy)benzeneHCID 10515879(S)-Benzyl 1-(methoxy(methyl)amino)-1-oxopropan-2-ylcarbamateHCID 178418918HCID 178418918, compound

Product 1

HCID 86704636HCID 86704636, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of the commercially available benzyl {(2S)-1-[methoxy(methyl)amino]-1-oxopropan-2-yl}carbamate (5.52 g, 20.75 mmol) and 1-bromo-3-(trifluoromethoxy)benzene (5 g, 20.75 mmol) in THF (100 ml) cooled in an ice/methanol/dry ice cooling bath was added isopropylmagnesium chloride (20.75 ml, 41.5 mmol) dropwise under nitrogen while internal temperature was maintained between −35 and −15° C. (monitored w/ an immersed temperature probe). After addition, the reaction was stirred cold and allowed to warm to ambient overnight. The reaction crude was then cooled to −20° C. and slowly quenched into a stirred mixture of crushed ice and HCl (1N, ice bath cool). The resulting mixture was worked up with brine, extracted with ethyl acetate, dried over Na2SO4, filtered and evaporated under reduced pressure. The pot residue was purified by flash chromatography (SiO2, Biotage SNAP Cartridge, silica gel, KP-Sil, 100 g cartridge). The column was eluted by an ethyl acetate/hexanes mixture (0% to 40% ethyl acetate). Related fractions were pooled and concentrated in vacuo to afford a colorless oil of 3.9824 g as the titled compound. LCMS calc.=367.1. found=390.00 (M+Na)+.

Workup

  1. temperaturewas maintained between −35 and −15° C. (monitored w/ an immersed temperature probe)
  2. additionAfter addition
  3. temperatureto warm to ambient overnight
  4. customThe reaction crude
  5. customslowly quenched into a stirred mixture of crushed ice and HCl (1N, ice bath cool)
  6. extractionextracted with ethyl acetate
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated under reduced pressure
  10. customThe pot residue was purified by flash chromatography (SiO2, Biotage SNAP Cartridge, silica gel, KP-Sil, 100 g cartridge)
  11. washThe column was eluted by an ethyl acetate/hexanes mixture (0% to 40% ethyl acetate)
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3909931bc48b4a3a9f51f4b752e18e62
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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