Sodium hydride → Tert-butyl 6-((methoxycarbonyl)methoxy)-5-(benzyloxy)-2-methoxypyrimidine-4-carboxylate

HRID 1497035Notes

Reaction equation

HRID 1497035 reaction equation
[CH2:1]([O:8][C:9]1[C:14](=[O:15])[NH:13][C:12]([O:16][CH3:17])=[N:11][C:10]=1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:28][C:29]([O:31][CH3:32])=[O:30]>CN(C=O)C>[CH2:1]([O:8][C:9]1[C:10]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[N:11][C:12]([O:16][CH3:17])=[N:13][C:14]=1[O:15][CH2:28][C:29]([O:31][CH3:32])=[O:30])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 136338080tert-Butyl 5-(benzyloxy)-2-methoxy-6-oxo-1,6-dihydropyrimidine-4-carboxylate

Product 1

HCID 89853159Tert-butyl 6-((methoxycarbonyl)methoxy)-5-(benzyloxy)-2-methoxypyrimidine-4-carboxylateYield 29.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

tert-Butyl 5-(benzyloxy)-2-methoxy-6-oxo-1,6-dihydropyrimidine-4-carboxylate (300 mg, 0.903 mmol) and sodium hydride (36.1 mg, 0.903 mmol) were stirred in anhydrous DMF (903 μl) at 0° C. under argon for 30 min. Methyl 2-bromoacetate (83 μl 0.90 mmol) was added and the mixture was stirred at rt for 3 h. The reaction was carefully quenched with water at 0° C. The reaction mixture was extracted with EtOAc (3×). The combined organic layers were washed with water, brine, dried over Na2SO4, concentrated and purified by flash chromatography (hexanes/EtOAc, eluted at ca. 30% EtOAc) to give tert-butyl 5-(benzyloxy)-2-methoxy-6-(2-methoxy-2-oxoethoxy)pyrimidine-4-carboxylate (109 mg, 0.270 mmol, 29.9% yield) as a colorless oil and Example 267A (117 mg, 0.289 mmol, 32.1% yield) as a colorless oil. 1H NMR (500 MHz, chloroform-d) δ 7.49-7.44 (m, 2H), 7.37-7.32 (m, 2H), 7.32-7.27 (m, 1H), 5.12 (s, 2H), 4.74 (s, 2H), 4.00 (s, 3H), 3.75 (s, 3H), 1.51 (s, 9H). LC-MS (ESI) 349.0 (M+H-t-Bu), retention time=2.07 min (Method B).

Workup

  1. customThe reaction was carefully quenched with water at 0° C
  2. extractionThe reaction mixture was extracted with EtOAc (3×)
  3. washThe combined organic layers were washed with water, brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. custompurified by flash chromatography (hexanes/EtOAc, eluted at ca. 30% EtOAc)

Sources & evidence

ORD record
ord-c8d2064f5dfb4ddfbe865f5bec26eadd
Source dataset
uspto-grants-2015_12
Patent number
US09199946B2

Reaction notes

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