Ethanol → methyl 4-[(1S)-1-[[(3R)-1,2,3,4-tetrahydroisoquinoline-3-carbonyl]amino]ethyl]benzoate

HRID 2205304Notes

Reaction equation

HRID 2205304 reaction equation
C(O)C.C(Cl)(=O)C.[CH3:8][O:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([C@@H:18]([NH:20][C:21]([C@H:23]2[CH2:32][C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH2:25][N:24]2C(OC(C)(C)C)=O)=[O:22])[CH3:19])=[CH:14][CH:13]=1)=[O:11]>C(OCC)(=O)C>[CH2:25]1[C:26]2[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:32][C@H:23]([C:21]([NH:20][C@H:18]([C:15]2[CH:14]=[CH:13][C:12]([C:10]([O:9][CH3:8])=[O:11])=[CH:17][CH:16]=2)[CH3:19])=[O:22])[NH:24]1

Participants

5

Reactant 3

HCID 702EthanolHCID 6367Acetyl chlorideHCID 131735812tert-butyl (3R)-3-[[(1S)-1-(4-methoxycarbonylphenyl)ethyl]carbamoyl]-3,4-dihydro-1H-isoquinoline-2-carboxylate

Product 1

HCID 117706205methyl 4-[(1S)-1-[[(3R)-1,2,3,4-tetrahydroisoquinoline-3-carbonyl]amino]ethyl]benzoateYield 95%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

Cool a mixture of ethyl acetate (214 mL) and ethanol (87.6 mL, 1.51 mol) to 0° C., and then add acetyl chloride (97.4 mL, 1.37 mol) in a dropwise fashion. Stir the mixture for 30 minutes while allowing it to warm to room temperature. Add a solution of tert-butyl (3R)-3-[[(1S)-1-(4-methoxycarbonylphenyl)ethyl]carbamoyl]-3,4-dihydro-1H-isoquinoline-2-carboxylate (60 g, 137 mmol) in ethyl acetate (480 mL), and then stir the resulting mixture at 40° C. overnight. Cool the mixture to room temperature, then isolate the resulting precipitate by filtration, and dry under reduced pressure. Add water (300 mL) to the solid, and then add a 32% aqueous ammonia solution until the pH of the mixture reaches 10. Isolate the suspended solids by filtration, then dry them in a vacuum oven at 45° C. overnight to furnish the title compound as a white solid (44 g, 95% yield). Mass spectrum (m/z): 339 ([M+H]+), 677 ([2M+H]+), 699 ([2M+Na]+).

Workup

  1. temperatureCool
  2. stirringstir the resulting mixture at 40° C. overnight
  3. temperatureCool the mixture to room temperature
  4. customisolate the resulting precipitate
  5. filtrationby filtration
  6. customdry under reduced pressure
  7. additionAdd water (300 mL) to the solid, and then add a 32% aqueous ammonia solution until the pH of the mixture
  8. customIsolate the suspended solids
  9. filtrationby filtration
  10. customdry them in a vacuum oven at 45° C. overnight

Sources & evidence

ORD record
ord-3c47e4c47e2f40f6b8897e343d0b4bc1
Source dataset
uspto-grants-2016_06
Patent number
US09371289B2

Reaction notes

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