Methanol → Methyl 5-oxo-5,6,7,8-tetrahydronaphthalene-1-carboxylate

HRID 1004445Notes

Reaction equation

HRID 1004445 reaction equation
[CH3:1][OH:2].CC(C)(C)CCN[C:8]([C:10]1[C:19]2[CH2:18][CH2:17][CH:16](CCN3CCC(C4C=CC=CC=4)CC3)[C:15](=[O:34])[C:14]=2[CH:13]=[CH:12][CH:11]=1)=[O:9].C(N(CC)CC)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN(C=O)C>[CH3:1][O:2][C:8]([C:10]1[C:19]2[CH2:18][CH2:17][CH2:16][C:15](=[O:34])[C:14]=2[CH:13]=[CH:12][CH:11]=1)=[O:9]

Participants

7

Reactant 3

HCID 887MethanolHCID 8471TriethylamineHCID 18794702N-(3,3-Dimethylbutyl)-5,6,7,8-tetrahydro-6-[2-(4-phenyl-1-piperidinyl)ethyl]-5-oxo-1-naphthalenecarboxamide

Product 1

HCID 12284900Methyl 5-oxo-5,6,7,8-tetrahydronaphthalene-1-carboxylateYield 90%

Reagents, catalysts & solvents 3

HCID 812191,3-Bis(diphenylphosphino)propaneCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A 450-mL Parr bomb was charged with methanol (81 mL), DMF (160 mL), compound 2 (24.0 g, 81.6 mmol), palladium acetate (549 mg, 2.45 mmol), 1,3-bis(diphenylphosphino)-propane (1.01 g, 2.45 mmol), and triethylamine (23 mL, 163 mmol). The bomb was purged with carbon monoxide using 2 fill/vent cycles. The bomb was repressurized to 150 psi and was heated to 80° C. for 3 hours. During this time additional CO was admitted to maintain the pressure at 150 psi. The bomb was cooled to room temperature and vented. A second identical run was made. The combined reactions were diluted with methylene chloride (2 L), washed with water (4×800 mL), dried (MgSO4) and concentrated in vacuo to a black solid. Chromatography (flash, silica, 120 mm dia×20 cm, 2% ethyl acetate/methylene chloride) provided semi-pure product. Recrystallization of this material from hot hexanes in 2 crops followed by chromatography of the final mothor liquors (silica gel, methylene chloride (700 mL) then 2% ethyl acetate/methylene chloride) provided a total of 30.3 g (90%) of the title compound.

Workup

  1. customThe bomb was purged with carbon monoxide using 2 fill/vent cycles
  2. temperatureto maintain the pressure at 150 psi
  3. temperatureThe bomb was cooled to room temperature
  4. additionThe combined reactions were diluted with methylene chloride (2 L)
  5. washwashed with water (4×800 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo to a black solid
  8. customChromatography (flash, silica, 120 mm dia×20 cm, 2% ethyl acetate/methylene chloride) provided semi-pure product
  9. customRecrystallization of this material from hot hexanes in 2 crops

Sources & evidence

ORD record
ord-b5391f0ba54b4f22a602f601305abfca
Source dataset
uspto-grants-2000_04
Patent number
US06048877

Reaction notes

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