Hydrochloric Acid → HCID 67439985, compound

HRID 2045587Notes

Reaction equation

HRID 2045587 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]([C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=1)[C:18](O)=[O:19])[C:9]([CH3:25])([CH3:24])[CH2:8]2)=[O:4].ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.Cl.CN1CCOCC1.[CH3:55][O:56][CH2:57][CH2:58][NH2:59].[BH4-].[Na+]>ClCCl.CO.C(OCC)(=O)C>[CH3:55][O:56][CH2:57][CH2:58][NH:59][C:18]([C:17]1[CH:16]=[C:15]([CH:10]2[C:9]([CH3:25])([CH3:24])[CH2:8][C:7]3[C:12](=[CH:13][CH:14]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:6]=3)[NH:11]2)[CH:23]=[CH:22][CH:21]=1)=[O:19]

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 80182-MethoxyethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 4311764Sodium borohydrideHCID 674419763-(6-(Methoxycarbonyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinolin-2-yl)benzoic acid

Product 1

HCID 67439985HCID 67439985, compoundYield 85.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 3-(6-(methoxycarbonyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinolin-2-yl)benzoic acid (100 mg, 0.30 mmol.) in dichloromethane (6.7 mL) was added N-hydroxybenzotriazole (59.7 mg, 0.44 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide.hydrochloric acid (169.7 mg, 0.44 mmol.), followed by 4-methylmorpholine (89.5 mg, 0.89 mmol) and the resultant mixture was stirred at room temperature for 1 h. Then 2-methoxyethanamine (26.6 mg, 0.44 mmol) was added to the flask and the reaction mixture was stirred under nitrogen overnight. Thin layer chromatography (petroleum ether:ethyl acetate=1:1) and LC-MS showed the reaction was complete. The reaction was quenched with water and extracted with dichloromethane (twice). The combined organic layers were washed with 2% sodium hydroxide aqueous solution (twice) and water (3 times), dried over anhydrous sodium sulfate. Removal of the solvent in vacuo gave 130 mg of crude product as a yellow oil, which was dissolved in methanol (3 mL) and treated with sodium borohydride (20 mg, 0.53 mmol) for an additional 3 h. LC-MS showed the reaction was complete. The reaction was quenched with water and extracted with ethyl acetate, dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to afford crude product, which was further purified by column chromatography (petroleum ether:ethyl acetate=1:1) from methanol to give 100 mg of methyl 2-(3-(2-methoxy ethylcarbamoyl)phenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylate as a white crystal. Yield: 85.6%.

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with dichloromethane (twice)
  3. washThe combined organic layers were washed with 2% sodium hydroxide aqueous solution (twice) and water (3 times)
  4. dry with materialdried over anhydrous sodium sulfate
  5. customRemoval of the solvent in vacuo
  6. customgave 130 mg of crude product as a yellow oil, which
  7. customThe reaction was quenched with water
  8. extractionextracted with ethyl acetate
  9. dry with materialdried over anhydrous sodium sulfate
  10. customThe solvent was removed under reduced pressure
  11. customto afford crude product, which
  12. customwas further purified by column chromatography (petroleum ether:ethyl acetate=1:1) from methanol

Sources & evidence

ORD record
ord-2cc942d972554280ae3d982834269e45
Source dataset
uspto-grants-2013_11
Patent number
US08586747B2

Reaction notes

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