4-Nitrophenyl chloroformate → (+)-5-Methoxycarbonyl-4-methoxymethyl-1,2,3,6-tetrahydro 2-oxo-6-(3,4-difluorophenyl)-1-[(4-nitrophenyloxy)carbonyl]pyrimidine

HRID 2085435Notes

Reaction equation

HRID 2085435 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH3:11][O:12][C:13]([C:15]1[CH:20]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[C:23]([F:28])[CH:22]=2)[NH:19][C:18](=[O:29])[NH:17][C:16]=1[CH2:30][O:31][CH3:32])=[O:14].Cl[C:34]([O:36][C:37]1[CH:42]=[CH:41][C:40]([N+:43]([O-:45])=[O:44])=[CH:39][CH:38]=1)=[O:35]>C1COCC1>[CH3:11][O:12][C:13]([C:15]1[CH:20]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[C:23]([F:28])[CH:22]=2)[N:19]([C:34]([O:36][C:37]2[CH:38]=[CH:39][C:40]([N+:43]([O-:45])=[O:44])=[CH:41][CH:42]=2)=[O:35])[C:18](=[O:29])[NH:17][C:16]=1[CH2:30][O:31][CH3:32])=[O:14]

Participants

5

Reactant 3

HCID 821294-Nitrophenyl chloroformateHCID 2733832Lithium HexamethyldisilazideHCID 108050354-(3,4-Difluoro-phenyl)-6-methoxymethyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid methyl ester

Product 1

HCID 10672264(+)-5-Methoxycarbonyl-4-methoxymethyl-1,2,3,6-tetrahydro 2-oxo-6-(3,4-difluorophenyl)-1-[(4-nitrophenyloxy)carbonyl]pyrimidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of lithium hexamethyldisilazide in THF (1M, 18.0 mL, 18.0 mmol) was added over 2-3 min. to a solution of (+)-5-methoxycarbonyl-4-methoxymethyl-1,2,3,6-tetrahydro-2-oxo-6-(3,4-difluorophenyl)-pyrimidine (1.98 g, 6.34 mmol) in anhydrous THF (20 mL) at −78° C. under argon atmosphere and the mixture was stirred for 10 min. The resulting solution was added over 6 min., via a cannula, to a stirred solution of 4-nitrophenyl chloroformate (4.47 g, 22.2 mmol) in THF (20 mL) at −78° C. The mixture was stirred for an additional 10 min. and the mixture was poured onto ice (50 g) and extracted with chloroform (2×50 mL). The combined extracts were dried (sodium sulfate) and the solvent evaporated. The residue was purified by flash chromatography (hexanes/ethyl acetate, 4/1 to 3.5/1), giving the product as a yellow syrup, which on trituration with hexanes became a white powder (2.40 g, 79%). 1H NMR δ 3.52 (s, 3H), 3.74 (s, 3H) 4.65-4.80 (q, J=16.5 Hz, 2H), 6.32 (s, 1H), 7.10-7.30 (m, 4H), 7.36 (d, J=9 Hz, 2H), 8.27 (d, J=9 Hz, 2H).

Workup

  1. stirringThe mixture was stirred for an additional 10 min.
  2. additionthe mixture was poured onto ice (50 g)
  3. extractionextracted with chloroform (2×50 mL)
  4. dry with materialThe combined extracts were dried (sodium sulfate)
  5. customthe solvent evaporated
  6. customThe residue was purified by flash chromatography (hexanes/ethyl acetate, 4/1 to 3.5/1)

Sources & evidence

ORD record
ord-9d621da0a4574db5a0cca1f41a0a5fca
Source dataset
uspto-grants-2004_04
Patent number
US06720324B2

Reaction notes

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