3-(3-Methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)isonicotinaldehyde → 5-(4-(cyclopropyl(hydroxy)methyl)pyridin-3-yl)-3-methylbenzo[d]oxazol-2(3H)-one

HRID 1253941Notes

Reaction equation

HRID 1253941 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[CH3:6][N:7]1[C:11]2[CH:12]=[C:13]([C:16]3[CH:17]=[N:18][CH:19]=[CH:20][C:21]=3[CH:22]=[O:23])[CH:14]=[CH:15][C:10]=2[O:9][C:8]1=[O:24]>C1COCC1>[CH:1]1([CH:22]([OH:23])[C:21]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[C:13]2[CH:14]=[CH:15][C:10]3[O:9][C:8](=[O:24])[N:7]([CH3:6])[C:11]=3[CH:12]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 866633583-(3-Methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)isonicotinaldehydeHCID 178418630HCID 178418630, compound

Product 1

HCID 667977715-(4-(cyclopropyl(hydroxy)methyl)pyridin-3-yl)-3-methylbenzo[d]oxazol-2(3H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Cyclopropylmagnesium bromide (0.5 M in THF, 3.5 mL, 1.8 mmol) was added dropwise to a solution of 3-(3-Methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-pyridine-4-carbaldehyde (150 mg, 0.58 mmol) in THF (1.6 mL) at −36′C. The resulting mixture was stirred at this temperature for 3 h, and the reaction was quenched by the addition of saturated NH4Cl solution. The mixture was diluted with ethyl acetate and water. The organic layer was separated and dried over anhydrous Na2SO4. After filtration and concentration, the residue was purified by flash column (MeOH/DCM, v/v, 0-4%) to give the title compound. (67 mg, 39%); ESI-MS m/z 297.2 [M+1]+, Retention time 1.00 min; 1HNMR (CDCl3, 400.342 MHz) δ ppm −0.27-0 (m, 1H), 0.36-0.45 (m, 2H), 0.52-0.57 (m, 1H), 0.96-1.02 (m, 1H), 3.47 (s, 3H), 4.52 (d, J=7.6 Hz, 1H), 7.14 (dd, J=8, 1.6 Hz, 1H), 7.25 (d, J=1.6 Hz, 1H), 7.33 (d, J=: 8 Hz, 1H), 8.18 (d, J=6 Hz, 1H), 8.47 (s, 1H), 8.63 (d, J=6 Hz, 1H).

Workup

  1. customthe reaction was quenched by the addition of saturated NH4Cl solution
  2. additionThe mixture was diluted with ethyl acetate and water
  3. customThe organic layer was separated
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationAfter filtration and concentration
  6. customthe residue was purified by flash column (MeOH/DCM, v/v, 0-4%)

Sources & evidence

ORD record
ord-634773b2f5974b31aecd42f932ca8b71
Source dataset
uspto-grants-2013_06
Patent number
US08455522B2

Reaction notes

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