Sodium hydride → benzyl 4-[2-((3-bromopyridin-2-yl){[2-(trimethylsilyl)ethoxy]methyl}amino)-2-oxoethyl]-3,6-dihydropyridine-1(2H)-carboxylate

HRID 550398Notes

Reaction equation

HRID 550398 reaction equation
[H-].[Na+].[Br:3][C:4]1[C:5]([NH:10][C:11](=[O:29])[CH2:12][C:13]2[CH2:14][CH2:15][N:16]([C:19]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:20])[CH2:17][CH:18]=2)=[N:6][CH:7]=[CH:8][CH:9]=1.[CH3:30][Si:31]([CH3:38])([CH3:37])[CH2:32][CH2:33][O:34][CH2:35]Cl>C1COCC1>[Br:3][C:4]1[C:5]([N:10]([CH2:35][O:34][CH2:33][CH2:32][Si:31]([CH3:38])([CH3:37])[CH3:30])[C:11](=[O:29])[CH2:12][C:13]2[CH2:14][CH2:15][N:16]([C:19]([O:21][CH2:22][C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[O:20])[CH2:17][CH:18]=2)=[N:6][CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl ether2×HCID 59555280Benzyl 4-[2-[(3-bromopyridin-2-yl)amino]-2-oxoethyl}-3,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 59555191benzyl 4-[2-((3-bromopyridin-2-yl){[2-(trimethylsilyl)ethoxy]methyl}amino)-2-oxoethyl]-3,6-dihydropyridine-1(2H)-carboxylateYield 0.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil; 117 mg, 4.88 mol) was added in portions over 10 min to a solution of benzyl 4-{2-[(3-bromopyridin-2-yl)amino]-2-oxoethyl}-3,6-dihydropyridine-1(2H)-carboxylate (1.91 g, 4.43 mol) in THF (15 mL) at 0° C. After 0.5 h, 2-(trimethylsilyl)ethoxymethyl chloride (0.861 mL, 4.88 mol) was then added slowly, keeping the temperature of the reaction mixture below 10° C. After 4 h, sodium hydride (60 mg) and 2-(trimethylsilyl)ethoxymethyl chloride (0.45 ml) were added and the reaction allowed to warm to room temperature overnight. The reaction was quenched with saturated aqueous ammonium chloride and the mixture was extracted with CH2Cl2 (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated. The crude product was purified by silica gel chromatography, eluting with a gradient of 40 to 70% ethyl acetate:hexanes to give the title compound (1.51 g). MS: m/z=560.2 (M+1).

Workup

  1. customthe temperature of the reaction mixture below 10° C
  2. waitAfter 4 h
  3. customThe reaction was quenched with saturated aqueous ammonium chloride
  4. extractionthe mixture was extracted with CH2Cl2 (3×)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with a gradient of 40 to 70% ethyl acetate

Sources & evidence

ORD record
ord-718a88ad812b48fb9b413fda7d574ad0
Source dataset
uspto-grants-2011_05
Patent number
US07947678B2

Reaction notes

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