Phosphorus oxychloride → Methyl 4-(4-(chloromethyl)-5-methyloxazol-2-yl)benzoate

HRID 931411Notes

Reaction equation

HRID 931411 reaction equation
O=P(Cl)(Cl)[Cl:3].[CH3:6][C:7]1[N+:8]([O-])=[C:9]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=2)[O:10][C:11]=1[CH3:12]>C(Cl)Cl>[Cl:3][CH2:6][C:7]1[N:8]=[C:9]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=2)[O:10][C:11]=1[CH3:12]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 68278194Methyl 4-(4,5-Dimethyl-3-oxido-1,3-oxazol-2-yl)benzoate

Product 1

HCID 23076573Methyl 4-(4-(chloromethyl)-5-methyloxazol-2-yl)benzoateYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

POCl3 (2.23 mL, 24.3 mmol) was added dropwise to a stirred solution of N-oxide 1 (5.0 g, 20.2 mmol) in dry DCM (100 mL) and the mixture stirred at 40° C. for 16 h. The solution was poured into a slurry of ice/1 M NaOH solution (100 mL) and the mixture stirred for 10 min. The mixture was extracted with DCM (3×50 mL), the combined organic extract dried and the solvent evaporated. The residue was purified by column chromatography, eluting with 20% EtOAc/pet. ether, to give benzoate 2 (4.12 g, 77%) as a white powder: mp (EtOAc) 127-128° C.; 1H NMR (CDCl3) δ 8.06-8.12 (m, 4H, H-2, H-3, H-5, H-6), 4.56 (s, 2H, CH2Cl), 3.94 (s, 3H, OCH3), 2.45 (s, 3H, CH3); MS m/z 266.6 (MH+, 100%). Anal. calcd for C13H12ClNO3: C, 58.77; H, 4.55; N, 5.27. Found: C, 58.82; H, 4.43; N, 5.18%.

Workup

  1. stirringthe mixture stirred for 10 min
  2. extractionThe mixture was extracted with DCM (3×50 mL)
  3. extractionthe combined organic extract
  4. customdried
  5. customthe solvent evaporated
  6. customThe residue was purified by column chromatography
  7. washeluting with 20% EtOAc/pet. ether

Sources & evidence

ORD record
ord-71c5006b86f94a2383682de8def0e8d0
Source dataset
uspto-grants-2016_03
Patent number
US09296732B2

Reaction notes

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