Dimethyl acetylenedicarboxylate → Methyl 2-(2-bromo-4-fluorobenzyl)-5,6-dihydroxypyrimidine-4-carboxylate
Reaction equation
[OH-:1].[K+].Cl.[NH2:4]O.[Br:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[CH2:14][C:15]#[N:16].[C:17]([O:25][CH3:26])(=[O:24])[C:18]#[C:19][C:20](OC)=[O:21]>CO>[CH3:26][O:25][C:17]([C:18]1[N:16]=[C:15]([CH2:14][C:8]2[CH:9]=[CH:10][C:11]([F:13])=[CH:12][C:7]=2[Br:6])[NH:4][C:20](=[O:21])[C:19]=1[OH:1])=[O:24]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 60 °C
Procedure
A solution of potassium hydroxide (18.7 ml, 18.7 mmol) in methanol and hydroxylamine hydrochloride (18.7 ml, 18.7 mmol) in methanol were mixed, filtered and added to 2-(2-bromo-4-fluorophenyl)acetonitrile (1 g, 4.67 mmol) in MeOH and stirred at 60° C. for 24 h, evaporated to dryness. The residue was dissolved in chloroform (30.0 ml) and to this was added dimethyl but-2-ynedioate (730 mg, 5.14 mmol). The mixture was stirred at 60° C. for 24 h, cooled and evaporated to dryness. The residue was dissolved in xylene (10 ml) and heated at 120° C. for 2 h in microwave oven. The cooled residue was evaporated to dryness and then triturated with EtOAc, filtered and washed with Et2O to give the title compound as a brown solid (0.21 g; 12%). LCMS: m/z=358 (MH+).
Workup
- filtrationfiltered
- customevaporated to dryness
- dissolutionThe residue was dissolved in chloroform (30.0 ml)
- stirringThe mixture was stirred at 60° C. for 24 h
- temperaturecooled
- customevaporated to dryness
- dissolutionThe residue was dissolved in xylene (10 ml)
- temperatureheated at 120° C. for 2 h in microwave oven
- customThe cooled residue was evaporated to dryness
- customtriturated with EtOAc
- filtrationfiltered
- washwashed with Et2O
Sources & evidence
- ORD record
- ord-8daebbc6be314bdf9ec7ea58b95399cc
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08921388B2
Reaction notes
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