Hydrochloric Acid → tert-butyl (2S)-2-[(1-cyclohexyl-3,4-dihydroisoquinolin-2(1H)-yl)carbonyl]pyrrolidine-1-carboxylate

HRID 2383016Notes

Reaction equation

HRID 2383016 reaction equation
CN1CCOCC1.[C:8]([O:12][C:13]([N:15]1[CH2:22][CH2:21][CH2:20][C@H:16]1[C:17]([OH:19])=O)=[O:14])([CH3:11])([CH3:10])[CH3:9].C(Cl)(=O)C(C)(C)C.Cl.[CH:31]1([CH:37]2[C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[CH2:40][CH2:39][NH:38]2)[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1.Cl>ClCCCl.CCOC(C)=O>[CH:31]1([CH:37]2[C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[CH2:40][CH2:39][N:38]2[C:17]([C@@H:16]2[CH2:20][CH2:21][CH2:22][N:15]2[C:13]([O:12][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:14])=[O:19])[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-Methylmorpholine2×HCID 62493Pivaloyl chlorideHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 675358401-Cyclohexyl-1,2,3,4-tetrahydroisoquinoline hydrochloride

Product 1

HCID 68250501tert-butyl (2S)-2-[(1-cyclohexyl-3,4-dihydroisoquinolin-2(1H)-yl)carbonyl]pyrrolidine-1-carboxylateYield 109.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-methylmorpholine (0.873 mL) was added to a solution of 1-(tert-butoxycarbonyl)-L-proline (1.28 g) in 1,2-dichloroethane (10 mL) under ice-cooling, followed by further addition of pivaloyl chloride (0.734 mL). The reaction liquid was stirred for 1 hour, and N-methylmorpholine (1.09 mL) and 1-cyclohexyl-1,2,3,4-tetrahydroisoquinoline hydrochloride (1.00 g) were then added thereto. The mixture was stirred at room temperature for 15 hours. To the reaction solution were added EtOAc and an aqueous 1 M HCl solution. The organic layer was washed with water, a saturated aqueous sodium hydrogen carbonate solution, and saturated brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to obtain tert-butyl (2S)-2-[(1-cyclohexyl-3,4-dihydroisoquinolin-2(1H)-yl)carbonyl]pyrrolidine-1-carboxylate (1.79 g).

Workup

  1. temperaturecooling
  2. customThe reaction liquid
  3. stirringThe mixture was stirred at room temperature for 15 hours
  4. washThe organic layer was washed with water
  5. dry with materiala saturated aqueous sodium hydrogen carbonate solution, and saturated brine, dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-69100ad6c9b9474bb07d7b99a9c83556
Source dataset
uspto-grants-2012_09
Patent number
US08263607B2

Reaction notes

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