Methyl iodide → HCID 86755998, compound

HRID 370054Notes

Reaction equation

HRID 370054 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([O:18][CH3:19])=[C:13]([O:16][CH3:17])[CH:14]=2)[C@H:9]([N:20]([CH2:25][C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=2)[C:21]([O:23][CH3:24])=[O:22])[CH2:8][C@@H:7]1[CH3:40])=[O:5])[CH3:2].[CH3:41]I>O1CCCC1>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([O:18][CH3:19])=[C:13]([O:16][CH3:17])[CH:14]=2)[C@H:9]([N:20]([CH:25]([C:26]2[CH:27]=[C:28]([C:36]([F:37])([F:39])[F:38])[CH:29]=[C:30]([C:32]([F:35])([F:33])[F:34])[CH:31]=2)[CH3:41])[C:21]([O:23][CH3:24])=[O:22])[CH2:8][C@@H:7]1[CH3:40])=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 6328Methyl iodideHCID 86755999HCID 86755999, compound

Product 1

HCID 86755998HCID 86755998, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a pre-dried flask under nitrogen atmosphere was added cis-4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester (0.200 g, 0.346 mmol) and tetrahydrofuran (2 mL). The solution was cooled to -78° C. and a 1.83 M solution of n-butyl lithiumin hexanes (0.23 g, 0.41 mmol) was added. The reaction was stirred at -78° C. for 45 min, then methyl iodide (0.026 mL, 0.41 mmol) was added and the reaction was warmed to 0° C. and stirred for 90 min. The reaction was quenched with saturated ammonium chloride solution, and the mixture was extracted three times with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo to give crude product. Purification by silica gel chromatography using 20% ethyl acetate/hexanes, followed by 70% ether/hexanes as eluent afforded the desired methylated product. MS m/z 593 (M+ +H); 1H NMR (CDCl3) δ 7.85 (bs, 1H), 7.8 (bs, 2H), 7.05 (bs, 1H), 6.5 (bs, 1H), 3.9 (s, 3H), 3.85 (s, 3H), 1.65 (d, 1.5H, J=7 Hz), 1.05 (d, 1.5H, J=7.0 Hz).

Workup

  1. temperaturethe reaction was warmed to 0° C.
  2. stirringstirred for 90 min
  3. customThe reaction was quenched with saturated ammonium chloride solution
  4. extractionthe mixture was extracted three times with dichloromethane
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give crude product
  9. customPurification by silica gel chromatography
  10. customafforded the

Sources & evidence

ORD record
ord-59fcfc18cf134369aa84b3d5ac820229
Source dataset
uspto-grants-2000_10
Patent number
US06140342

Reaction notes

Loading…