Sodium hydride → N-[2-(Trimethylsilyl)ethoxymethyl]-4-[[(5,6,7,8-tetrahydro-5,5-dimethyl-8-oxo-2-naphthalenyl)amino]carbonyl]benzoic acid, methyl ester

HRID 265428Notes

Reaction equation

HRID 265428 reaction equation
[CH3:1][C:2]1([CH3:26])[CH2:11][CH2:10][C:9](=[O:12])[C:8]2[CH:7]=[C:6]([NH:13][C:14]([C:16]3[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=3)=[O:15])[CH:5]=[CH:4][C:3]1=2.[H-].[Na+].[H][H].[CH3:31][Si:32]([CH3:39])([CH3:38])[CH2:33][CH2:34][O:35][CH2:36]Cl>CN(C)C=O.C(=O)(O)[O-].[Na+]>[CH3:31][Si:32]([CH3:39])([CH3:38])[CH2:33][CH2:34][O:35][CH2:36][N:13]([C:6]1[CH:5]=[CH:4][C:3]2[C:2]([CH3:26])([CH3:1])[CH2:11][CH2:10][C:9](=[O:12])[C:8]=2[CH:7]=1)[C:14]([C:16]1[CH:17]=[CH:18][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:24][CH:25]=1)=[O:15]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 537129964-[[(5,6,7,8-Tetrahydro-5,5-dimethyl-8-oxo-2-naphthalenyl)amino]carbonyl]benzoic acid methyl esterHCID 178418361HCID 178418361, compound

Product 1

HCID 20706778N-[2-(Trimethylsilyl)ethoxymethyl]-4-[[(5,6,7,8-tetrahydro-5,5-dimethyl-8-oxo-2-naphthalenyl)amino]carbonyl]benzoic acid, methyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of 4-[[(5,6,7,8-tetrahydro-5,5-dimethyl-8-oxo-2-naphthalenyl)amino]carbonyl]benzoic acid, methyl ester (5.07 g, 14.4 mmol) in anhydrous N,N-dimethylformamide (75 mL) at 0° C. was treated with 80% sodium hydride (477 mg, 15.9 mmoles). When hydrogen evolution ceased 2-(trimethylsilyl)ethoxymethyl chloride (3.61 g, 21.7 mmol) was slowly added. After 16 h at room temperature, the mixture was diluted with a 10% sodium bicarbonate solution (100 mL) and extracted with diethyl ether. The organic phase was concentrated in vacuo and the residue chromatographed (eluted with 20% ethyl acetate in hexane) over silica to give 4.24 g (Y: 61%) of the title product; MS (DCI) m/e: 482 (MH+); 1H-NMR (CDCl3): δ 7.90 (d, J=7.5 Hz, 2H), 7.82 (s, 1H), 7.45 (d, J=7.5 Hz, 2H), 7.25 (m, 2H), 5.22 (bs, 2H), 3.93 (s, 3H), 3.67 (t, J=8.0 Hz, 2H), 2.69 (t, J=7.0 Hz, 2H), 1.98 (t, J=7.0 Hz, 2H), 1.33 (s, 6H), 0.96 (t, J=8.0 Hz, 2H), 0.00 (s, 9H).

Workup

  1. additionwas slowly added
  2. extractionextracted with diethyl ether
  3. concentrationThe organic phase was concentrated in vacuo
  4. customthe residue chromatographed
  5. wash(eluted with 20% ethyl acetate in hexane) over silica

Sources & evidence

ORD record
ord-9b0ab9e49c2d4c4998a36b53d01274c1
Source dataset
uspto-grants-1997_07
Patent number
US05648385

Reaction notes

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