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

HRID 1664800Notes

Reaction equation

HRID 1664800 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.Cl[CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36]>O1CCCC1>[Br:3][C:4]1[C:5]([N:10]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[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 60.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (60% dispersion in oil; 0.20 g, 5.0 mmol) was slowly added 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 mmol) in tetrahydrofuran (15 mL) at 0° C. After 30 min, [2-(chloromethoxy)ethyl](trimethyl)silane (0.86 mL, 4.88 mmol) was added. After 4 h, additional sodium hydride (60% dispersion in oil; 0.10 g, 2.5 mmol) was added, followed by [2-(chloromethoxy)ethyl](trimethyl)silane (0.43 mL, 2.44 mmol). After 18 h, the reaction mixture was quenched with saturated ammonium chloride. The mixture was extracted with dichloromethane. The combined organic extracts were dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (60% hexanes/ethyl acetate→30% hexanes/ethyl acetate) gave the title compound (1.51 g). MS 560.1 (M).

Workup

  1. waitAfter 4 h
  2. waitAfter 18 h
  3. customthe reaction mixture was quenched with saturated ammonium chloride
  4. extractionThe mixture was extracted with dichloromethane
  5. dry with materialThe combined organic extracts were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (60% hexanes/ethyl acetate→30% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-e2de36d8667f4af7a55aa63275117a12
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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