Water → HCID 86756033, compound

HRID 1937471Notes

Reaction equation

HRID 1937471 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([O:20][CH3:21])=[C:15]([CH2:18][OH:19])[CH:16]=2)[C@H:11]([N:22]([CH2:27][C:28]2[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:29]=2)[C:23]([O:25][CH3:26])=[O:24])[CH2:10][C@@H:9]1[CH3:42])=[O:7])[CH3:4].I[CH3:44].O>CN(C)C=O>[CH2:3]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([O:20][CH3:21])=[C:15]([CH2:18][O:19][CH3:44])[CH:16]=2)[C@H:11]([N:22]([CH2:27][C:28]2[CH:29]=[C:30]([C:38]([F:39])([F:41])[F:40])[CH:31]=[C:32]([C:34]([F:35])([F:36])[F:37])[CH:33]=2)[C:23]([O:25][CH3:26])=[O:24])[CH2:10][C@@H:9]1[CH3:42])=[O:7])[CH3:4]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86756027HCID 86756027, compound

Product 1

HCID 86756033HCID 86756033, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of sodium hydride (4.2 mg, 60% dispersion in mineral oil, 0.10 mmol) in N,N-dimethylformamide (2.5 mL) was added cis-4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-7-hydroxymethyl-6-methoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester (Example 85) (50 mg, 0.087 mmol). After the reaction was stirred at room temperature for 30 min, iodomethane (60 μL, 0.96 mmol) was added, and the reaction was stirred for 18 h. The reaction mixture was then poured into water and extracted with ethyl acetate (2×20 mL). The combined organic extracts were dried over magnesium sulfate, filtered and concentrated in vacuo. The excess N,N-dimethylformamide was azeotroped off with heptanes. Purification by silica gel chromatography using 15-25% ethyl acetate/hexanes as eluent afforded the title product (30 mg, 59%): 1H NMR (CDCl3) δ 1.1 (d, 3H), 1.3 (t, 3H), 3.4 (s, 3H), 3.75 (s, 3H), 3.8 (s, 3H), 6.4 (s, 1H), 7.4 (s, 1H), 7.75 (s, 2H), 7.8 (s, 1H).

Workup

  1. stirringthe reaction was stirred for 18 h
  2. extractionextracted with ethyl acetate (2×20 mL)
  3. dry with materialThe combined organic extracts were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe excess N,N-dimethylformamide was azeotroped off with heptanes
  7. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-96d9ac0b0e934c53b763ca051a86d9ba
Source dataset
uspto-grants-2002_05
Patent number
US06395751B1

Reaction notes

Loading…