Hydrochloric Acid → 2-Naphthalenamine, 1,2,3,4-tetrahydro-5-methoxy-N-propyl-, hydrochloride (1:1), (2S)-

HRID 875248Notes

Reaction equation

HRID 875248 reaction equation
[ClH:1].[CH3:2][O:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][CH:8]([NH2:14])[CH2:9]2.[C:15]([O-])(=O)[CH3:16].[Na+].[C:20](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+].Cl>O1CCCC1.C(O)(=O)C>[ClH:1].[CH3:2][O:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][C@H:8]([NH:14][CH2:20][CH2:15][CH3:16])[CH2:9]2

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 517045Sodium AcetateHCID 5049666Sodium triacetoxyborohydrideHCID 122805722-amino-5-methoxytetralin HCl

Product 1

HCID 247544052-Naphthalenamine, 1,2,3,4-tetrahydro-5-methoxy-N-propyl-, hydrochloride (1:1), (2S)-Yield 78%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A 2 L reactor with double jacket temperature control was charged with 5-methoxy-2-aminotetraline hydrochloride (Xa) (161 g), sodium acetate (62 g), and tetrahydrofuran (750 mL). The suspension was stirred at 0° C. To that suspension were added glacial acetic acid (22 mL), sodium triacetoxyborohydride (200 g) and propionalhedyde (XIa) (48 g diluted with 50 mL of tetrahydrofuran via a dropping funnel maintaining the mass temperature below 10° C. The resulting suspension was stirred overnight at 0° C. To that suspension was slowly added a 25% solution of sodium hydroxide (250 mL) at 0° C. and the resulting mixture was let to warm up to room temperature under stirring for 30 minutes. The aqueous layer was discarded and the organic layer was washed with a 6.25% solution of sodium hydroxide (200 mL). The aqueous layer was discarded and the organic layer was heated at 50° C. To this solution concentrated hydrochloric acid (77 mL) was added over 20 minutes and the resulting thick suspension was diluted with 150 mL of tetrahydrofuran. The suspension is maintained at 50° C. for 30 minutes then rapidly cooled to 10° C. and stirred at 10° C. for 30 minutes. The product was isolated by filtration, washed 2 times with cold THF (2×200 mL) and dried under vacuum at 40° C. until constant weight to give N-Propyl MAT.HCl salt as an white solid with 78% yield.

Workup

  1. temperaturemaintaining the mass temperature below 10° C
  2. stirringThe resulting suspension was stirred overnight at 0° C
  3. temperatureto warm up to room temperature
  4. stirringunder stirring for 30 minutes
  5. washthe organic layer was washed with a 6.25% solution of sodium hydroxide (200 mL)
  6. temperaturethe organic layer was heated at 50° C
  7. additionTo this solution concentrated hydrochloric acid (77 mL) was added over 20 minutes
  8. additionthe resulting thick suspension was diluted with 150 mL of tetrahydrofuran
  9. temperatureThe suspension is maintained at 50° C. for 30 minutes
  10. temperaturethen rapidly cooled to 10° C.
  11. stirringstirred at 10° C. for 30 minutes
  12. customThe product was isolated by filtration
  13. washwashed 2 times with cold THF (2×200 mL)
  14. customdried under vacuum at 40° C. until constant weight
  15. customto give N-Propyl MAT

Sources & evidence

ORD record
ord-1beefc5b92a64b53b7ff0c3dff720b08
Source dataset
uspto-grants-2015_03
Patent number
US08981121B2

Reaction notes

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