Oxalyl chloride → 3-[(1-Methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)-5-[(phenylmethyl)oxy]benzamide

HRID 1989899Notes

Reaction equation

HRID 1989899 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:13]=1)[C:8]([OH:10])=O)[CH3:3].C(Cl)(=O)C(Cl)=O.[CH3:28][N:29]1[CH:33]=[CH:32][C:31]([NH2:34])=[N:30]1>CN(C=O)C.C(Cl)Cl.C(N(CC)CC)C>[CH3:3][CH:2]([O:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:13]=1)[C:8]([NH:34][C:31]1[CH:32]=[CH:33][N:29]([CH3:28])[N:30]=1)=[O:10])[CH3:1]

Participants

7

Reactant 3

HCID 65578Oxalyl chlorideHCID 1372541-Methyl-3-aminopyrazoleHCID 534011033-Benzyloxy-5-isopropoxybenzoic acid

Product 1

HCID 536296253-[(1-Methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)-5-[(phenylmethyl)oxy]benzamideYield 99.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 8471TriethylamineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

DMF (2 drops) was added to a solution of 3-[(1-methylethyl)oxy]-5-[(phenylmethyl)oxy]benzoic acid (40.0 g, 0.14 mol) and oxalyl chloride (14.6 mL, 0.17 mol) in DCM (700 mL) The mixture was stirred at ambient temperature for 4 hours and the DCM and excess oxalyl chloride evaporated in vacuo. The residual acid chloride was dissolved in DCM (300 mL) and added dropwise to 1-methyl-3-aminopyrazole (14.25 g, 0.147 mol) and triethylamine (41 mL, 0.29 mmol) in DCM (300 mL), at 0° C. Stirred at ambient temperature for 24 hours. The DCM was evaporated in vacuo, and the residue partitioned between ethyl acetate (400 mL) and 1N hydrochloric acid (200 mL). The ethyl acetate layer was washed sequentially with saturated aqueous sodium hydrogen carbonate (200 mL) and brine (100 mL), dried (MgSO4) and evaporated in vacuo. The residue was chromatographed on silica, eluting with a gradient of 50% ethyl acetate in isohexane, to give the desired compound (51 g). 1H NMR δ (CDCl3): 1.30 (d, 6H), 3.61 (s, 3H), 4.50 (sept, 1H), 5.01 (s, 2H), 6.66 (m, 1H), 6.88 (m, 1H), 7.00 (m, 1H), 7.06 (m, 1H), 7.24 (m, 1H), 7.39 (m, 5H), 9.50 (s, 1H). m/z 366 (M+H)+

Workup

  1. customthe DCM and excess oxalyl chloride evaporated in vacuo
  2. dissolutionThe residual acid chloride was dissolved in DCM (300 mL)
  3. stirringStirred at ambient temperature for 24 hours
  4. customThe DCM was evaporated in vacuo
  5. customthe residue partitioned between ethyl acetate (400 mL) and 1N hydrochloric acid (200 mL)
  6. washThe ethyl acetate layer was washed sequentially with saturated aqueous sodium hydrogen carbonate (200 mL) and brine (100 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated in vacuo
  9. customThe residue was chromatographed on silica
  10. washeluting with a gradient of 50% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-3c3b7eaec90248e78b4bbf2b7758b1bb
Source dataset
uspto-grants-2010_01
Patent number
US07642263B2

Reaction notes

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