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

HRID 1609924Notes

Reaction equation

HRID 1609924 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:15])=[C:11]([CH3:14])[N+:12]=2[O-])=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:18])=O>C(Cl)(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:15])=[C:11]([CH2:14][Cl:18])[N:12]=2)=[CH:4][CH:3]=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-methyloxazoleYield 72%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A solution of 2-(4-bromophenyl)-4,5-dimethyl-oxazole-3-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 stir at reflux for 30 min. The reaction was then cooled to rt 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% EtOAc/hexanes; 1H NMR (500 MHz, CDCl3) δ 7.88-7.86 (m, 2H), 7.59-7.56 (m, 2H), 4.54 (s, 2H), 2.42 (s, 3H); 13C (125 MHz, CDCl3) δ 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) λmax 281 nm (ε 21349); HRMS (FAB) m/z calc'd for C11H1079BrClNO: 285.9634, found 285.9641; Anal. Calc'd 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-e95ea200436c44889c0fc3b1319e96a1
Source dataset
uspto-grants-2006_01
Patent number
US06982278B2

Reaction notes

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