Triethylamine → tert-butyl (3R)-3-[[(1S)-1-(4-methoxycarbonylphenyl)ethyl]carbamoyl]-3,4-dihydro-1H-isoquinoline-2-carboxylate

HRID 2205303Notes

Reaction equation

HRID 2205303 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:17]([C:18](O)=[O:19])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.ClC(OCC(C)C)=O.[NH2:36][C@H:37]([C:39]1[CH:48]=[CH:47][C:42]([C:43]([O:45][CH3:46])=[O:44])=[CH:41][CH:40]=1)[CH3:38]>ClCCl>[CH3:46][O:45][C:43]([C:42]1[CH:47]=[CH:48][C:39]([C@@H:37]([NH:36][C:18]([C@H:17]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH2:9][N:8]2[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[O:19])[CH3:38])=[CH:40][CH:41]=1)=[O:44]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 688607(3R)-2-[(tert-butoxy)carbonyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acidHCID 17751895Methyl 4-((1S)-1-aminoethyl)benzoate

Product 1

HCID 131735812tert-butyl (3R)-3-[[(1S)-1-(4-methoxycarbonylphenyl)ethyl]carbamoyl]-3,4-dihydro-1H-isoquinoline-2-carboxylateYield 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. mixture of (3R)-2-tert-butoxycarbonyl-3,4-dihydro-1H-isoquinoline-3-carboxylic acid (40.0 g, 141.4 mmol) and dichloromethane (784 mL), add triethylamine (21.7 mL, 155.5 mmol). Then add isobutyl chloroformate (20.3 mL, 155.5 mmol) in a dropwise fashion. After the end of the addition, stir the mixture at 0° C. for 20 minutes. Then, add methyl (S)-4-(1-aminoethyl)benzoate (27.9 g, 155.5 mmol), and stir the mixture at room temperature for 1 hour. Add water (400 mL), separate the layers, and wash the organic layer with 1 M aqueous KHSO4 (500 mL), followed by saturated aqueous NaHCO3 (500 mL). Dry the organic phase over MgSO4, filter to remove the solids, and concentrate the filtrate under reduced pressure to furnish the title compound as a white solid (60 g, 97% yield). Mass spectrum (m/z): 339 ([M+H−Boc]+), 383 ([M+H−t-Bu]+), 439 ([M+H]+).

Workup

  1. additionAfter the end of the addition
  2. stirringstir the mixture at room temperature for 1 hour
  3. customAdd water (400 mL), separate the layers
  4. washwash the organic layer with 1 M aqueous KHSO4 (500 mL)
  5. dry with materialDry the organic phase over MgSO4
  6. filtrationfilter
  7. customto remove the solids
  8. concentrationconcentrate the filtrate under reduced pressure

Sources & evidence

ORD record
ord-b6249fa7f1934afca45498f0dc0f3cce
Source dataset
uspto-grants-2016_06
Patent number
US09371289B2

Reaction notes

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