1-Bromo-3,5-bis(trifluoromethyl)benzene → HCID 11589807, compound

HRID 604593Notes

Reaction equation

HRID 604593 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].[F:20][C:21]([F:34])([F:33])[C:22]1[CH:23]=[C:24](Br)[CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1.C([Mg]Cl)(C)C>C1COCC1>[F:20][C:21]([F:33])([F:34])[C:22]1[CH:23]=[C:24]([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:25]=[C:26]([C:28]([F:29])([F:30])[F:31])[CH:27]=1

Participants

5

Reactant 3

HCID 676021-Bromo-3,5-bis(trifluoromethyl)benzeneHCID 10515879(S)-Benzyl 1-(methoxy(methyl)amino)-1-oxopropan-2-ylcarbamateHCID 178418918HCID 178418918, compound

Product 1

HCID 11589807HCID 11589807, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

Benzyl {(1S)-2-[methoxy(methyl)amino]-1-methyl-2-oxoethyl}carbamate (6 kg, 22.5 mol) and 3,5-bis(trifluoromethyl)bromobenzene (4.85 L, 28.1 mol) are dissolved in anhydrous THF (24 L). The solution is purged with nitrogen to remove distilled oxygen. The solution is cooled to −10° C. and i-PrMgCl in THF (56.4 mol) is slowly added (2 h) to the reaction via addition funnel, maintaining a reaction temperature ≦−5° C. The solution is allowed to warm to 20° C. and aged overnight at 20° C. The reaction is then cooled to −10° C. under nitrogen and is quenched slowly over 2 h into 5N HCl (14 L) that is maintained at 0-5° C. MTBE (60 L) is added and the biphasic mixture is agitated for 5 min. After warming to 20-25° C., it is allowed to settle for 30 min, and then the layers are separated. The organic layer is washed with water twice (12 L).

Workup

  1. customThe solution is purged with nitrogen
  2. customto remove
  3. distillationdistilled oxygen
  4. customto the reaction
  5. additionvia addition funnel
  6. temperaturemaintaining a reaction temperature ≦−5° C
  7. temperatureto warm to 20° C. and aged overnight at 20° C
  8. temperatureThe reaction is then cooled to −10° C. under nitrogen
  9. customis quenched slowly over 2 h into 5N HCl (14 L) that
  10. temperatureis maintained at 0-5° C
  11. additionMTBE (60 L) is added
  12. temperatureAfter warming to 20-25° C.
  13. waitto settle for 30 min
  14. customthe layers are separated
  15. washThe organic layer is washed with water twice (12 L)

Sources & evidence

ORD record
ord-60039142a34f44f99fea86444cd8a56b
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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