Hydrochloric Acid → N-(5-(3-(N-Methylamino)propyloxy)-2-methylphenyl)-tricyclo[3.3.1.13,7]decane-1-acetamide, hydrochloride

HRID 1066256Notes

Reaction equation

HRID 1066256 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[OH:13][C:14]1[CH:15]=[CH:16][C:17]([CH3:34])=[C:18]([NH:20][C:21](=[O:33])[CH2:22][C:23]23[CH2:32][CH:27]4[CH2:28][CH:29]([CH2:31][CH:25]([CH2:26]4)[CH2:24]2)[CH2:30]3)[CH:19]=1.O[CH2:36][CH2:37][CH2:38][N:39](C)[C:40](=O)OC(C)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[ClH:67]>O1CCCC1.CO>[ClH:67].[CH3:40][NH:39][CH2:38][CH2:37][CH2:36][O:13][C:14]1[CH:15]=[CH:16][C:17]([CH3:34])=[C:18]([NH:20][C:21](=[O:33])[CH2:22][C:23]23[CH2:32][CH:27]4[CH2:26][CH:25]([CH2:31][CH:29]([CH2:28]4)[CH2:30]2)[CH2:24]3)[CH:19]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11776Triphenylphosphine3×HCID 220568ethyl N-ethoxycarbonyliminocarbamate3×HCID 9904389N-(5-Hydroxy-2-methylphenyl)-tricyclo[3.3.1.13,7]decane-1-acetamideHCID 10375241tert-Butyl (3-hydroxypropyl)methylcarbamate

Product 1

HCID 131722598N-(5-(3-(N-Methylamino)propyloxy)-2-methylphenyl)-tricyclo[3.3.1.13,7]decane-1-acetamide, hydrochloride

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Diethyl azodicarboxylate (0.50 ml) was added to a solution of N-(5-hydroxy-2-methylphenyl)-tricyclo[3.3.1.13,7]decane-1-acetamide (0.50 g, Example 12), tert-butyl N-(3-hydroxypropyl)-N-methylcarbamate (0.60 g, J. Org. Chem., 1988, 53(10), 2229) and triphenylphosphine (0.88 g) in tetrahydrofuran (5 ml). After stirring for 19 hours at room temperature further triphenylphosphine (0.90 g) and diethyl azodicarboxylate (0.50 ml) were added. After stirring for 4 hours at room temperature further triphenylphosphine (0.90 g) and diethyl azodicarboxylate (0.50 ml) were added and the reaction mixture was stirred for 3 days. The reaction was then concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with dichloromethane:ethyl acetate (9:1) to give material that was further purified by chromatography over a Dynamax® column using a Gilson automated chromatography machine eluting with iso-hexane:ethyl acetate (4:1) to give the Mitsunobu reaction product (0.29 g) which was dissolved in methanol (10 ml). A solution of hydrogen chloride (generated by slow addition of acetyl chloride (12 ml) to methanol (10 ml) at 0° C. CARE—Very Exothermic) was then added to the latter solution and the reaction stirred at room temperature for 1 hour. The reaction was then concentrated under reduced pressure to give the title compound as a yellow solid (0.13 g).

Workup

  1. additionwere added
  2. additionwere added
  3. concentrationThe reaction was then concentrated under reduced pressure
  4. customthe residue was purified by silica gel chromatography
  5. washeluting with dichloromethane:ethyl acetate (9:1)
  6. customto give material that
  7. customwas further purified by chromatography over a Dynamax® column
  8. washeluting with iso-hexane:ethyl acetate (4:1)
  9. customto give
  10. stirringthe reaction stirred at room temperature for 1 hour
  11. concentrationThe reaction was then concentrated under reduced pressure

Sources & evidence

ORD record
ord-a5ff58e146f0438498071b49349dae6d
Source dataset
uspto-grants-2001_06
Patent number
US06242470B1

Reaction notes

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