Toluene → HCID 76694873, compound

HRID 1867256Notes

Reaction equation

HRID 1867256 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH:8]3[CH:11]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:12]([C:14]([N:16]([O:18][CH3:19])[CH3:17])=[O:15])=[N:13][N:7]3[C:6]=2[CH:26]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:37]1(C)[CH:42]=CC=C[CH:38]=1.C(Br)C=C>C1COCC1>[CH2:42]([C:11]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:8]2[CH2:9][O:10][C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:26][C:6]=3[N:7]2[N:13]=[C:12]1[C:14]([N:16]([O:18][CH3:19])[CH3:17])=[O:15])[CH:37]=[CH2:38]

Participants

6

Reactant 4

HCID 1140TolueneHCID 7841Allyl bromideHCID 2733832Lithium HexamethyldisilazideHCID 86624791HCID 86624791, compound

Product 1

HCID 76694873HCID 76694873, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

8-Chloro-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (4-1; a racemic mixture, 0.43 g, 1.1 mmol) was dissolved in anhydrous THF (10 mL) and cooled to −78° C. in an acetone/dry ice bath under an N2 atmosphere. The resulting solution was treated with LHMDS (1.39 mL of a 1M toluene solution, 1.39 mmol) and stirred 2 minutes to produce a deep red color. Allyl bromide (0.20 mL, 2.2 mmol) was added neat and the solution was allowed to stir 10 minutes at −78° C. and then removed from the ice bath. Upon reaching ambient temperature, the reaction was judged complete by TLC and quenched by at addition of sat. aqueous NH4Cl (10 mL). The mixture was extracted with Et2O (3×10 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified using flash column chromatography (ISCO Redisep 40 g SiO2 column, 0-40% EtOAc/hexanes gradient) to provide pure 3-allyl-8-chloro-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (4-2; a racemic mixture): 1H NMR (300 MHz, CDCl3) δ 7.42-7.15 (m, 6H), 6.77 (m, 2H), 5.83 (m, 1H), 5.27 (dd, J=16.9, 1.1 Hz, 1H), 5.21 (d, J=10.0 Hz, 1H), 4.10 (dd, J=10.3, 3.7 Hz, 1H), 3.90 (s, 3H), 3.63 (dd, J=11.0, 3.6 Hz, 1H), 3.35 (dd, J=13.4, 6.0 Hz, 1H), 3.32 (s, 3H), 2.96 (m, 2H); MS (M+H+, C22H22ClN3O3) 412.3 found 412.9 required.

Workup

  1. customto produce a deep red color
  2. stirringto stir 10 minutes at −78° C.
  3. customremoved from the ice bath
  4. customUpon reaching ambient temperature
  5. customquenched by at addition of sat. aqueous NH4Cl (10 mL)
  6. extractionThe mixture was extracted with Et2O (3×10 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude residue was purified

Sources & evidence

ORD record
ord-8967733caf9943789cc82f475d88eb64
Source dataset
uspto-grants-2009_12
Patent number
US07632833B2

Reaction notes

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