Ammonia → (S)-2-t-Butoxycarbonyl-3-hydroxymethyl-7-hydroxyoctahydroisoquinoline

HRID 2306893Notes

Reaction equation

HRID 2306893 reaction equation
C(O)(C)(C)C.N.[C:7]([O:11][C:12]([N:14]1[C@H:23]([CH2:24][OH:25])[CH2:22][C:21]2[C:16](=[CH:17][C:18]([OH:26])=[CH:19][CH:20]=2)[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].[Li].[NH4+].[Cl-]>CCOCC>[C:7]([O:11][C:12]([N:14]1[C@H:23]([CH2:24][OH:25])[CH2:22][CH:21]2[CH:16]([CH2:17][CH:18]([OH:26])[CH2:19][CH2:20]2)[CH2:15]1)=[O:13])([CH3:10])([CH3:8])[CH3:9]

Participants

7

Reactant 5

HCID 222Ammonia2×HCID 6386tert-ButanolHCID 25517Ammonium ChlorideHCID 3028194LithiumHCID 69917915(S)-2-t-Butoxycarbonyl-1,2,3,4-tetrahydro-3-hydroxymethyl-7-hydroxyisoquinoline

Product 1

HCID 69917878(S)-2-t-Butoxycarbonyl-3-hydroxymethyl-7-hydroxyoctahydroisoquinoline

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of t-butyl alcohol (9.1 g, 123 mmol), 50 ml ether, and ammonia (150 mL) is added (S)-2-t-butoxycarbonyl-1,2,3,4-tetrahydro-3-hydroxymethyl-7-hydroxyisoquinoline (5 mmol). The solution is brought to reflux, and lithium shot (0.51 g, 82 mmol) is added over 30 minutes. The solution is allowed to reflux for 3 hours, and solid NH4Cl added until the color disappears. The ammonia is allowed to evaporate overnight, ice-water is added, and the organic layer separated. The aqueous layer is extracted with chloroform and the combined organic phases are washed with brine, dried and evaporated. The crude product is redissolved in methanol, 5% Pt/C added and the solution shaken under 3 atm H2 for 6 hours to complete the reduction. The catalyst is filtered and the solvent evaporated. The resulting residue is purified by silica gel flash column chromatography to give the title compound.

Workup

  1. temperatureto reflux
  2. additionis added over 30 minutes
  3. temperatureto reflux for 3 hours
  4. customto evaporate overnight
  5. additionice-water is added
  6. customthe organic layer separated
  7. extractionThe aqueous layer is extracted with chloroform
  8. washthe combined organic phases are washed with brine
  9. customdried
  10. customevaporated
  11. dissolutionThe crude product is redissolved in methanol
  12. addition5% Pt/C added
  13. filtrationThe catalyst is filtered
  14. customthe solvent evaporated
  15. customThe resulting residue is purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-0fa0b1e24c964079a87e7530d5875c33
Source dataset
uspto-grants-2004_12
Patent number
US06828427B1

Reaction notes

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