Phosphorus oxychloride → 2-(4-Bromophenyl)-4-(chloromethyl)-5-methyloxazole

HRID 398099Notes

Reaction equation

HRID 398099 reaction equation
[CH3:1][C:2]1[N+:3]([O-])=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([Br:14])=[CH:10][CH:9]=2)[O:5][C:6]=1[CH3:7].P(Cl)(Cl)([Cl:18])=O>C(Cl)(Cl)Cl>[Br:14][C:11]1[CH:12]=[CH:13][C:8]([C:4]2[O:5][C:6]([CH3:7])=[C:2]([CH2:1][Cl:18])[N:3]=2)=[CH:9][CH:10]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 109015972-(4-Bromophenyl)-4,5-dimethyloxazole 3-oxide

Product 1

HCID 109571082-(4-Bromophenyl)-4-(chloromethyl)-5-methyloxazole

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A solution of 4,5-dimethyl-2-(4-bromophenyl)-oxazole oxide (96.6 g, 0.36 mol) in CHCl3 (0.90 L) was treated dropwise with phosphorous oxychloride (61.1 g, 0.40 mol) allowing the reaction to exotherm and then was stirred at reflux for 30 min. The reaction was then cooled to room temperature and washed with water (2×1 L). The combined aqueous washes were back extracted with CH2Cl2 (2×400 mL). The organic layers were dried (MgSO4), and the solvent removed in vacuo to give crude product that was recrystallized from hot hexanes (300 mL), decanting the hot supernate away from a dark oily material. The remaining dark oil was agitated in additional hot hexanes (200 mL) and the combined supernates were cooled to 0° C. to crystallize the product which was isolated by filtration to give 74.2 g (72%) of 2-(4-bromophenyl-4-(chloromethyl)-5-methyloxazole as a lime-green powder: Rf=0.39 in 20% ethyl acetate/hexanes; 1H NMR (500 MHz, CDCl3) 7.88-7.86 (m, 2H), 7.59-7.56 (m, 2H), 4.54 (s, 2H), 2.42 (s, 3H); 13C (125 MHz, CDCl3) 159.2, 146.9, 133.2, 132.0, 127.6, 126.1, 124.7,37.1, 11.5; IR (KBr) 2970, 1633, 1599, 1481, 1401, 1258, 1117, 1008 cm−1; UV (EtOH)max281 nm (21349); HRMS (FAB) m/z calculated for C11H1079BrClNO: 285,9634, found 285.9641; Anal. Calculated for C11H9ClBrNO: C, 46.11; H, 3.17; N, 4.89; Cl, 12.37; Br, 27.88. Found C, 46.28; H 3.07; N, 4.81; Cl, 12.36; Br, 27.88.

Workup

  1. customthe reaction
  2. temperatureat reflux for 30 min
  3. washwashed with water (2×1 L)
  4. extractionThe combined aqueous washes were back extracted with CH2Cl2 (2×400 mL)
  5. dry with materialThe organic layers were dried (MgSO4)
  6. customthe solvent removed in vacuo
  7. customto give crude product that
  8. customwas recrystallized from hot hexanes (300 mL)
  9. customdecanting the hot supernate away from a dark oily material
  10. stirringThe remaining dark oil was agitated in additional hot hexanes (200 mL)
  11. temperaturethe combined supernates were cooled to 0° C.
  12. customto crystallize the product which
  13. customwas isolated by filtration

Sources & evidence

ORD record
ord-15bec8d6a40743a6a5a9ce77e0cfdac6
Source dataset
uspto-grants-2003_08
Patent number
US06610696B2

Reaction notes

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