Pyridine → HCID 69833698, compound

HRID 370038Notes

Reaction equation

HRID 370038 reaction equation
[CH2:1]([O:3][C:4](=[O:28])[N:5]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C@H:6]1[C:15]2[C:10](=[CH:11][C:12]([O:18][CH3:19])=[C:13]([O:16][CH3:17])[CH:14]=2)[NH:9][C@@H:8]([CH3:20])[CH2:7]1)[CH3:2].N1C=CC=CC=1.Cl[C:36]([O:38][CH3:39])=[O:37].[OH-].[K+]>ClCCl.O>[CH3:39][O:38][C:36]([N:9]1[C:10]2[C:15](=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=2)[C@H:6]([N:5]([CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:4]([O:3][CH2:1][CH3:2])=[O:28])[CH2:7][C@@H:8]1[CH3:20])=[O:37]

Participants

7

Reactant 4

HCID 1049PyridineHCID 6586Methyl chloroformateHCID 14797Potassium HydroxideHCID 69832857HCID 69832857, compound

Product 1

HCID 69833698HCID 69833698, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of cis-benzyl-(6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl)-carbamic acid ethyl ester (Example 66) (111 mg, 0.29 mmol) in anhydrous dichloromethane (2 mL), was treated sequentially with anhydrous pyridine (1 mL), and methyl chloroformate (38 μL, 0.49 mmol). After stirring at room temperature overnight, water (10 mL) and an aqueous 10% KOH solution (10 mL) were added, and the mixture was extracted with ethyl acetate (3×10 mL). The combined organic phases were then washed with 1N HCl (2×10 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 112 mg crude product. Purification by silica gel chromatography using 0-50% ethyl acetate/hexanes as eluent afforded the desired final product (12.6 mg, 10%): MS m/z 443 (M+ +1), 460 (M++ 18); 1H NMR (CDCl3) δ 7.02 (C8, s, 1H), 6.42 (C5, s, 1H).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×10 mL)
  2. washThe combined organic phases were then washed with 1N HCl (2×10 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give 112 mg crude product
  7. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-ea5212702dd74d8e891a9307587e7739
Source dataset
uspto-grants-2000_10
Patent number
US06140342

Reaction notes

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