Benzyl Alcohol → HCID 68621153, compound

HRID 1244696Notes

Reaction equation

HRID 1244696 reaction equation
[OH-].[K+].C(OC([CH:8]1[CH2:25][N:12]2[CH2:13][CH2:14][C:15]3[C:20]([CH:11]2[CH2:10][CH:9]1[N:26]([CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[CH:19][C:18]([O:21][CH3:22])=[C:17]([O:23][CH3:24])[CH:16]=3)=O)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C([N:51]([CH2:54]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:63])C=CC=CC=1.[CH2:73]([OH:80])[C:74]1[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=1>O.O1CCCC1.ClCCl>[CH2:73]([O:80][C:54](=[O:63])[NH:51][CH:8]1[CH2:25][N:12]2[CH2:13][CH2:14][C:15]3[C:20]([CH:11]2[CH2:10][CH:9]1[N:26]([CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[CH:19][C:18]([O:21][CH3:22])=[C:17]([O:23][CH3:24])[CH:16]=3)[C:74]1[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=1

Participants

9

Reactant 6

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 14797Potassium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 199401P,P-Diphenylphosphinic azideHCID 68620473HCID 68620473, compound

Product 1

HCID 68621153HCID 68621153, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

Potassium hydroxide pellets (86%, 1.53 g, 23.4 mmol) were added to a solution of (RS,RS,RS)-2-(benzyl-tert-butoxycarbonyl-amino)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinoline-3-carboxylic acid ethyl ester (1.20 g, 2.28 mmol) in water/tetrahydrofuran 1:1 (24 mL), and the mixture was heated at reflux for 72 h. After cooling, the solution was neutralized with 1 M aq. potassium phosphate buffer (pH 6.85) and extracted three times with dichloromethane. The organic layers were pooled, dried (MgSO4), and evaporated. The residue was suspended in toluene (24 mL) and treated with triethylamine (230 mg, 2.28 mmol) and diphenylphosphoryl azide (659 mg, 2.28 mmol). The reaction was kept at r.t. for 90 min and heated at 80° C. for 90 min, then benzyl alcohol (369 mg, 3.41 mmol) was added, and the reaction temperature was kept at 100° C. for 18 h. The reaction mixture was diluted with dichloromethane and washed with 10% aq. citric acid solution, 1 M aq. sodium hydroxide solution, and brine, dried (MgSO4), and evaporated. Chromatography (SiO2, heptane/EtOAc gradient) afforded the title compound (805 mg, 59%). Light yellow foam, MS (ISP) 602.3 (M+H)+.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 72 h
  3. temperatureAfter cooling
  4. extractionextracted three times with dichloromethane
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. waitthe reaction temperature was kept at 100° C. for 18 h
  8. washwashed with 10% aq. citric acid solution, 1 M aq. sodium hydroxide solution, and brine
  9. dry with materialdried (MgSO4)
  10. customevaporated

Sources & evidence

ORD record
ord-5dc15129530248a4a469865d69966b62
Source dataset
uspto-grants-2006_10
Patent number
US07122555B2

Reaction notes

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