Water → HCID 86756033, compound

HRID 1857498Notes

Reaction equation

HRID 1857498 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 add 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-8a063b18b8014fd88d2b5241cdfd7026
Source dataset
uspto-grants-2000_11
Patent number
US06147090

Reaction notes

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