Hydrochloric Acid → Benzyl (3S)-3-(4-morpholinylmethyl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate

HRID 515886Notes

Reaction equation

HRID 515886 reaction equation
[N:1]1([C:7]([C@@H:9]2[CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][N:10]2[C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])=O)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl.C([O-])(O)=O.[Na+]>O1CCCC1>[N:1]1([CH2:7][C@@H:9]2[CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][N:10]2[C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 1118330Benzyl (3S)-3-(4-morpholinylcarbonyl)-3,4-dihydro-2(1H)-isoquinoline carboxylate

Product 1

HCID 118482909Benzyl (3S)-3-(4-morpholinylmethyl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5.3 g of the product obtained in Step A (13.9 mmol) in 278 mL of tetrahydrofuran there are added 14 mL of borane-dimethylsulphide complex (BH3Me2S) (27.8 mmol) at ambient temperature. The batch is heated for 4 hours at 80° C. It is allowed to return to ambient temperature and there are then added 7 mL (14 mmol) of BH3Me2S. The reaction mixture is again heated at 80° C. for 2 hours. The tetrahydrofuran is then evaporated off and then there is slowly added methanol and then 5.6 mL of 5N aqueous HCl solution (27.8 mmol). The mixture is stirred at ambient temperature overnight, and then at 80° C. for 1 hour. Saturated aqueous NaHCO3 solution is then added to the reaction mixture placed at 0° C. until a pH of 8 is obtained, and extraction with ethyl acetate is then carried out. The organic phase is then dried over MgSO4, and then filtered and evaporated to dryness. The title product is obtained in the form of an oil.

Workup

  1. customto return to ambient temperature
  2. additionthere are then added 7 mL (14 mmol) of BH3Me2S
  3. temperatureThe reaction mixture is again heated at 80° C. for 2 hours
  4. customThe tetrahydrofuran is then evaporated off
  5. waitat 80° C. for 1 hour
  6. customplaced at 0° C. until a pH of 8
  7. customis obtained
  8. extractionextraction with ethyl acetate
  9. dry with materialThe organic phase is then dried over MgSO4
  10. filtrationfiltered
  11. customevaporated to dryness

Sources & evidence

ORD record
ord-4fbe3ec00a064f2a8c6751dfb33595f9
Source dataset
uspto-grants-2015_08
Patent number
US09108983B2

Reaction notes

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