Hydrochloric Acid → 12-(Methanesulfonyl)-3-methoxy-5,8,8a,9,10,11,12,12a,13,13a-decahydro-6H-isoquinolino[2,1-g][1,6]naphthyridine--hydrogen chloride (1/1)

HRID 484396Notes

Reaction equation

HRID 484396 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:18]2[C@H:17]3[N:8]([C:9](=O)[C@@H:10]4[C@H:15]([CH2:16]3)[N:14]([S:21]([CH3:24])(=[O:23])=[O:22])[CH2:13][CH2:12][CH2:11]4)[CH2:7][CH2:6][C:5]=2[CH:4]=1.[BH4-].[Na+].B(F)(F)F.CCOCC.[ClH:37]>O1CCCC1>[ClH:37].[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:18]2[C@H:17]3[N:8]([CH2:9][C@@H:10]4[C@H:15]([CH2:16]3)[N:14]([S:21]([CH3:24])(=[O:23])=[O:22])[CH2:13][CH2:12][CH2:11]4)[CH2:7][CH2:6][C:5]=2[CH:4]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8000Boron trifluoride etherateHCID 4311764Sodium borohydrideHCID 10451421(8aS,12aS,13aS)-3-methoxy-12-methanesulfonyl-5,6,8a,9,10,11,12,12a,13,13a-decahydroisoquino[2,1-g][1,6]naphthyridin-8-one

Product 1

HCID 16889812-(Methanesulfonyl)-3-methoxy-5,8,8a,9,10,11,12,12a,13,13a-decahydro-6H-isoquinolino[2,1-g][1,6]naphthyridine--hydrogen chloride (1/1)

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

A slurry of 4.894 Kg of (8aS,12aS,13aS)-3-methoxy-12-methanesulfonyl-5,6,8a,9,10,11,12,12a, 13,13a-decahydroisoquino[2,1-g][1,6]naphthyridin-8-one (7) in 60 Kg of tetrahydrofuran was stirred with 1.103 Kg of sodium borohydride at about 10° C. This mixture was maintained at 10° C. while 5.836 Kg of boron trifluoride etherate was added. Upon completion of the addition the reaction mixture was refluxed for 30 minutes, cooled to 20° C., and 67 litres of 1N hydrochloric acid added cautiously. The majority of the solvent was then removed by distillation at atmospheric pressure, the residue cooled to below 30° C. and aqueous 6N sodium hydroxide solution added until the pH reached 12.2 (about 35 litres). The reaction mixture was then extracted with methylene chloride, and the combined extracts washed with water. The solvent was removed by distillation at atmospheric pressure, replacing the methylene chloride with ethanol until the pot temperature reached 78° C. The solution was then cooled to about 70° C. and concentrated aqueous hydrochloric acid (1.3 litres) was added. The slurry was stirred at about 70° C. for 10 minutes, cooled to 20° C. and then stood for 12 hours The product was filtered, washed with 33 Kg of cold ethanol and dried under vacuum at 40°-45° C., giving (8aR,12aS,13aS)-3-methoxy-12-methanesulfonyl-5,6,8a,9,10,11,12,12a,13,13a-decahydro-8H-isoquino[2,1-g][1,6]naphthyridine hydrochloride, m.p. 257°-258° C.

Workup

  1. additionwas added
  2. additionUpon completion of the addition the reaction mixture
  3. temperaturewas refluxed for 30 minutes
  4. customThe majority of the solvent was then removed by distillation at atmospheric pressure
  5. temperaturethe residue cooled to below 30° C.
  6. additionaqueous 6N sodium hydroxide solution added until the pH
  7. extractionThe reaction mixture was then extracted with methylene chloride
  8. washthe combined extracts washed with water
  9. customThe solvent was removed by distillation at atmospheric pressure
  10. customreached 78° C
  11. temperatureThe solution was then cooled to about 70° C.
  12. additionconcentrated aqueous hydrochloric acid (1.3 litres) was added
  13. temperaturecooled to 20° C.
  14. waitstood for 12 hours
  15. filtrationThe product was filtered
  16. washwashed with 33 Kg of cold ethanol
  17. customdried under vacuum at 40°-45° C.

Sources & evidence

ORD record
ord-af5b7dcbb7b1491cafa99b69356d45ba
Source dataset
uspto-grants-1993_07
Patent number
US05231181

Reaction notes

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