Pyridine → HCID 69832881, compound

HRID 370036Notes

Reaction equation

HRID 370036 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[C:20]2[C:15](=[CH:16][C:17]([O:23][CH3:24])=[C:18]([O:21][CH3:22])[CH:19]=2)[C@H:14]([NH:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:13][C@@H:12]1[CH3:33])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.Cl[C:41]([O:43][CH2:44][CH3:45])=[O:42].[OH-].[K+]>ClCCl.O>[CH2:1]([O:8][C:9]([N:11]1[C:20]2[C:15](=[CH:16][C:17]([O:23][CH3:24])=[C:18]([O:21][CH3:22])[CH:19]=2)[C@H:14]([N:25]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:13][C@@H:12]1[CH3:33])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 10928Ethyl chloroformateHCID 14797Potassium HydroxideHCID 70168750HCID 70168750, compound

Product 1

HCID 69832881HCID 69832881, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of cis-4-benzylamino-6,7-dimethyoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid benzyl ester (Example 2B) (150 mg, 0.34 mmol) in anhydrous dichloromethane (5 mL) were added pyridine (0.20 mL, 2.3 mmol) and ethyl chloroformate (0.16 mL, 1.7 mmol). The reaction was stirred at room temperature overnight. The reaction mixture was then poured into water (20 mL), and aqueous 2N KOH (10 mL) was added. The solution was stirred for 30 min, then the mixture was extracted with ether (3×25 mL). The organic phases were combined and washed with 1N HCl (3×10 mL) and then a saturated sodium bicarbonate solution (10 mL). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to give 190 mg of crude product. Purification by silica gel chromatography using 0-40% ethyl acetate/hexanes as eluent afforded the desired final product (146 mg, 83%): MS m/z 519 (M+ +1), 537 (M+ +19), 340 (M+ -178); 1H NMR (CDCl3) δ 6.99 (C8, s, 1H), 6.42 (C5, s, 1H).

Workup

  1. additionwas added
  2. stirringThe solution was stirred for 30 min
  3. extractionthe mixture was extracted with ether (3×25 mL)
  4. washwashed with 1N HCl (3×10 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give 190 mg of crude product
  9. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-eab559736b7646fa8fd41be5409105eb
Source dataset
uspto-grants-2000_10
Patent number
US06140342

Reaction notes

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