Carbon Tetrachloride → Methyl 2-[1-[(2,5-dimethylphenyl)acetyl]-4-piperidinyl]-4,5-dihydro-4-oxazolecarboxylate

HRID 2043732Notes

Reaction equation

HRID 2043732 reaction equation
[CH3:1][O:2][C:3](=[O:27])[CH:4]([CH2:25]O)[NH:5][C:6]([CH:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:24])[CH2:15][C:16]2[CH:21]=[C:20]([CH3:22])[CH:19]=[CH:18][C:17]=2[CH3:23])[CH2:10][CH2:9]1)=[O:7].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)C(C)C)(C)C.C(Cl)(Cl)(Cl)Cl.C(=O)(O)[O-].[Na+]>C(#N)C.C(OCC)(=O)C.O.ClCCl>[CH3:23][C:17]1[CH:18]=[CH:19][C:20]([CH3:22])=[CH:21][C:16]=1[CH2:15][C:14]([N:11]1[CH2:10][CH2:9][CH:8]([C:6]2[O:7][CH2:25][CH:4]([C:3]([O:2][CH3:1])=[O:27])[N:5]=2)[CH2:13][CH2:12]1)=[O:24]

Participants

10

Reactant 5

HCID 5943Carbon TetrachlorideHCID 11776TriphenylphosphineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 67461522N-[[1-[(2,5-dimethylphenyl)acetyl]-4-piperidinyl]carbonyl]-DL-serine methyl ester2×

Product 1

HCID 67460115Methyl 2-[1-[(2,5-dimethylphenyl)acetyl]-4-piperidinyl]-4,5-dihydro-4-oxazolecarboxylate

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-[[1-[(2,5-dimethylphenyl)acetyl]-4-piperidinyl]carbonyl]-DL-serine methyl ester (i.e. the product of Example 9, Step C) (2.59 g, 6.88 mmol) in 25 mL of dry acetonitrile and 7 mL of dry dichloromethane was added triphenylphosphine (2.71 g, 10.32 mmol) and then N,N-diisopropylethylamine (1.6 g, 12.38 mmol). The reaction mixture was stirred until homogeneous, and carbon tetrachloride (1.59 g, 10.32 mmol) was added dropwise over 5 minutes. The reaction mixture was stirred for 2.5 h at room temperature, cooled to 0° C. and diluted with 50 mL of ethyl acetate followed by 15 mL of saturated aqueous sodium bicarbonate solution. The mixture was stirred for 10 minutes, poured into 40 mL of water, and the organic layer was separated, washed with brine, dried over MgSO4 and concentrated under reduced pressure to give 6 g of a yellow oil. The oil was purified by flash chromatography on silica gel using 50-100% of ethyl acetate in hexanes to give 900 mg of the title compound. 360 mg of starting amide was also recovered from the reaction mixture.

Workup

  1. additionwas added dropwise over 5 minutes
  2. temperaturecooled to 0° C.
  3. stirringThe mixture was stirred for 10 minutes
  4. customthe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-10304786c2a14b3fb7ba27cdd6dee3dd
Source dataset
uspto-grants-2013_11
Patent number
US08586611B2

Reaction notes

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