Benzyl Bromide → Ethyl 3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylate

HRID 348115Notes

Reaction equation

HRID 348115 reaction equation
[OH:1][C:2]1[C:11](=[O:12])[N:10]2[C:5]([C:6]([CH3:14])([CH3:13])[O:7][CH2:8][CH2:9]2)=[N:4][C:3]=1[C:15]([O:17][CH2:18][CH3:19])=[O:16].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOCC>[CH2:20]([O:1][C:2]1[C:11](=[O:12])[N:10]2[C:5]([C:6]([CH3:13])([CH3:14])[O:7][CH2:8][CH2:9]2)=[N:4][C:3]=1[C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 54708345Ethyl 3-hydroxy-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylate

Product 1

HCID 21069952Ethyl 3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylateYield 78%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of intermediate 25, ethyl 3-hydroxy-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylate, (2.68 g, 10 mmol) and benzyl bromide (1.43 mL, 12 mmol) in DMF (40 mL) was added K2CO3 (2.07 g, 20 mmol). After stirring 48 h at ambient temperature, the reaction mixture was diluted with ether (100 mL), then washed with water (3×30 mL) and brine (20 mL). The organic layer was dried (Na2SO4/activated carbon), filtered and concentrated to give a yellow solid. Trituration with hexanes/ether (9:1) afforded the title compound as an off-white solid (2.79 g, 78% yield). 1H NMR (500 MHz, CDCl3) δ ppm: 7.48–7.45 (2H, m), 7.37–7.30 (3H, m), 5.25 (2H, s), 4.33 (2H, q, J=7.3 Hz), 4.05–3.99 (4H, m), 1.62 (6H, s), 1.29 (3H, t, J=7.3 Hz). HRMS (M+H) calcd for C19H23N2O5: 359.1607; found: 359.1611. Anal calcd for C19H22N2O5: C, 63.67; H, 6.18; N, 7.81; found: C, 63.63; H, 6.16; N, 7.78.

Workup

  1. washwashed with water (3×30 mL) and brine (20 mL)
  2. dry with materialThe organic layer was dried (Na2SO4/activated carbon)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a yellow solid

Sources & evidence

ORD record
ord-d9aa892133004e449875dd2522fa2dc7
Source dataset
uspto-grants-2007_02
Patent number
US07176196B2

Reaction notes

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