Hydrochloric Acid → 6-(3,4-Difluorophenyl)-4-methyl-5-methoxycarbonyl-1-(4-nitrophenoxy)carbonyl-2-oxo-1,2,3,6-tetrahydro-pyrimidine

HRID 2085385Notes

Reaction equation

HRID 2085385 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([CH:10]2[N:15]([C:16]([O:18][C:19]3[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=3)=[O:17])[C:14]([O:28]C)=[N:13][C:12]([CH3:30])=[C:11]2[C:31]([O:33][CH3:34])=[O:32])[CH:6]=[CH:7][C:8]=1[F:9]>C1COCC1>[F:2][C:3]1[CH:4]=[C:5]([CH:10]2[N:15]([C:16]([O:18][C:19]3[CH:20]=[CH:21][C:22]([N+:25]([O-:27])=[O:26])=[CH:23][CH:24]=3)=[O:17])[C:14](=[O:28])[NH:13][C:12]([CH3:30])=[C:11]2[C:31]([O:33][CH3:34])=[O:32])[CH:6]=[CH:7][C:8]=1[F:9]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 10671680HCID 10671680, compound

Product 1

HCID 158957606-(3,4-Difluorophenyl)-4-methyl-5-methoxycarbonyl-1-(4-nitrophenoxy)carbonyl-2-oxo-1,2,3,6-tetrahydro-pyrimidineYield 93.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 10% aqueous HCl (5 mL) was added to a stirring solution of (+)-6-(3,4-difluorophenyl)-1,6-dihydro-2-methoxy-5-methoxycarbonyl-4-methyl-1-[(4-nitrophenyloxy)-carbonyl]pyrim-idine (4.10 g, 9.10 mmol) in THF (20 mL) at room temperature and the resulting solution was stirred overnight. The THF was removed in vacuo and the resulting residue was extracted with EtOAc (3×20 mL), washed with brine (10 mL) and then dried over Na2SO4. The solvent was removed in vacuo, giving (+)-6-(3,4-di-fluorophenyl)-1,6-dihydro-2-oxo-5-methoxycarbonyl-4-methyl-1-[(4-nitrophenyloxy)carbonyl]pyrimidine as a viscous oil (3.8 g, 8.5 mmol). The oil was dissolved in THF (20 mL) and 3-bromo-propylamine hydrobromide (2.33 g, 10.8 mmol) and NaHCO3 (1.81 g, 21.5 mmol) were added. The resulting suspension was stirred at room temperature overnight. The THF was removed in vacuo and the resulting residue was dissolved in water (10 mL) and then extracted with EtOAc (3×20 mL). The EtOAc extracts were combined, dried over Na2SO4, filtered and the solvent was removed, giving (+)-1-(3-bromopropylcarbamoyl)-6-(3,4-difluorophenyl)-4-methyl-2-oxo-1,6-dihydropyrimidine-5-carboxylic acid methyl ester (3.28 g, 83%): 1H NMR δ 2.05-2.15 (m, 2 H), 2.43 (s, 3 H), 3.40-3.56 (m, 4 H), 3.72 (s, 3 H), 6.69 (s, 1 H), 7.08-7.27 (m, 3 H), 7.57 (br s, 1 H), 8.84 (br t, 1 H). Anal. Calcd for C17H18N3O4 F2Br: C, 45.76; H, 4.07; N, 9.42. Found: C, 45.70; H, 3.99; N, 9.16.

Workup

  1. customThe THF was removed in vacuo
  2. extractionthe resulting residue was extracted with EtOAc (3×20 mL)
  3. washwashed with brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-1e6f4c6058a949f1bdb91bcfd8b55da3
Source dataset
uspto-grants-2004_04
Patent number
US06720324B2

Reaction notes

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