Sodium hydride → tert-butyl 2-methoxyethyl((4-oxo-4,5,7,8-tetrahydro-3H-pyrano[4,3-d]pyrimidin-2-yl)methyl)carbamate

HRID 713467Notes

Reaction equation

HRID 713467 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9].[H-].[Na+].Cl[CH2:16][C:17]1[NH:18][C:19](=[O:27])[C:20]2[CH2:26][O:25][CH2:24][CH2:23][C:21]=2[N:22]=1>O1CCCC1>[C:8]([O:7][C:6](=[O:12])[N:5]([CH2:4][CH2:3][O:2][CH3:1])[CH2:16][C:17]1[NH:18][C:19](=[O:27])[C:20]2[CH2:26][O:25][CH2:24][CH2:23][C:21]=2[N:22]=1)([CH3:9])([CH3:11])[CH3:10]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 11788575Tert-butyl N-(2-methoxyethyl)carbamateHCID 1357419472-(Chloromethyl)-7,8-dihydro-3H-pyrano[4,3-D]pyrimidin-4(5H)-one

Product 1

HCID 136612914tert-butyl 2-methoxyethyl((4-oxo-4,5,7,8-tetrahydro-3H-pyrano[4,3-d]pyrimidin-2-yl)methyl)carbamateYield 49.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 2-methoxyethylcarbamate (185 mg, 1.06 mmol) in anhydrous tetrahydrofuran (5 mL) was added sodium hydride (95%, 127 mg, 4.28 mmol) portion-wise slowly, followed by 2-(chloromethyl)-7,8-dihydro-3H-pyrano[4,3-d]pyrimidin-4(5H)-one (212 mg, 1.6 mmol). The reaction mixture was stirred for 48 h. The reaction was quenched with water (approximately 3 mL) and the solvent evaporated. The residue was re-dissolved in acetonitrile and purified by column chromatography (100% dichloromethane for 5 min, then slow gradient up to 15% methanol in dichloromethane). The resulting clear oil was dissolved with 0.5 mL of acetonitrile and heated in vacuo to give the title compound as a white solid (179 mg). 1H NMR (400 MHz, chloroform-d) 8 ppm 4.60 (s, 2H) 4.21-4.34 (m, 2H) 3.91-4.01 (m, 3H) 3.66-3.79 (m, 2H) 3.51-3.66 (m, 6H) 2.71-2.80 (m, 2H) 1.48 (s, 3H) 1.35 (s, 6H). MS (m/z, MH+): 340.4

Workup

  1. customThe reaction was quenched with water (approximately 3 mL)
  2. customthe solvent evaporated
  3. dissolutionThe residue was re-dissolved in acetonitrile
  4. custompurified by column chromatography (100% dichloromethane for 5 min
  5. dissolutionThe resulting clear oil was dissolved with 0.5 mL of acetonitrile
  6. temperatureheated in vacuo

Sources & evidence

ORD record
ord-ce2ca9c5b3194b8696c76dcd7ea8dab2
Source dataset
uspto-grants-2015_11
Patent number
US09181266B2

Reaction notes

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