Cesium carbonate → 4-(4-Chloro-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl)-benzoic acid tert-butyl ester

HRID 1373050Notes

Reaction equation

HRID 1373050 reaction equation
[CH3:1][C:2]1[C:3](=[O:10])[NH:4][C:5](=[O:9])[NH:6][C:7]=1[Cl:8].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:18][C:19]1[CH:31]=[CH:30][C:22]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[CH:21][CH:20]=1.ClCCl.CO>CN(C)C=O>[C:26]([O:25][C:23](=[O:24])[C:22]1[CH:21]=[CH:20][C:19]([CH2:18][N:4]2[C:3](=[O:10])[C:2]([CH3:1])=[C:7]([Cl:8])[NH:6][C:5]2=[O:9])=[CH:31][CH:30]=1)([CH3:29])([CH3:28])[CH3:27]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 3014023Thymine, 6-chloro-HCID 11414578Tert-butyl 4-(bromomethyl)benzoateHCID 21226129Dichloromethane methanol

Product 1

HCID 693740034-(4-Chloro-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ylmethyl)-benzoic acid tert-butyl esterYield 40.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Methyl-6-chloropyrimidine-2,4-dione (1.00 g, 6.22 mmol) was dissolved in dimethylformamide (15 mL).To the solution was added cesium carbonate (2.02 g, 6.22 mmol) and t-butyl 4-bromomethylbenzoate (1.69 g, 6.22 mmol). The mixture was stirred at room temperature for 20 hours. The solvent was evaporated under a vacuum at 60° C. The residue was mixed with tetrahydrofuran (50 mL) and methanol (10 mL) and filtered. The filtrate was evaporated in a vacuum to an amber oil. The oil was purified by flash chromatography on silica gel eluting first with dichloromethane then with dichloromethane:methanol (19:1) to give the desired product (0.88 g, 40% yield). 1H-NMR (DMSO-d6) δ 11.8 (s, 1H), 7.85 (d, 2H), 7.34 (d, 2H), 5.22 (s, 2H), 1.88 (s, 3H), 1.51 (s, 9H).

Workup

  1. customThe solvent was evaporated under a vacuum at 60° C
  2. additionThe residue was mixed with tetrahydrofuran (50 mL) and methanol (10 mL)
  3. filtrationfiltered
  4. customThe filtrate was evaporated in a vacuum to an amber oil
  5. customThe oil was purified by flash chromatography on silica gel eluting first with dichloromethane

Sources & evidence

ORD record
ord-eb8dabc316a54c8b8f05a76b86cfb603
Source dataset
uspto-grants-2007_01
Patent number
US07160893B2

Reaction notes

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