Carbon Tetrachloride → 1,1-Dimethylethyl 4-[4,5-dihydro-4-(methoxycarbonyl)-2-oxazolyl)-1-piperidinecarboxylate

HRID 2043725Notes

Reaction equation

HRID 2043725 reaction equation
O[CH2:2][CH:3]([NH:8][C:9]([CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:4]([O:6][CH3:7])=[O:5].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>[CH3:7][O:6][C:4]([CH:3]1[CH2:2][O:10][C:9]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[N:8]1)=[O:5]

Participants

10

Reactant 5

HCID 5943Carbon TetrachlorideHCID 11776TriphenylphosphineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 674637131,1-Dimethylethyl 4-[[(1-(hydroxymethyl)-2-methoxy-2-oxoethyl)amino]carbonyl]-1-piperidinecarboxylate2×

Product 1

HCID 674608611,1-Dimethylethyl 4-[4,5-dihydro-4-(methoxycarbonyl)-2-oxazolyl)-1-piperidinecarboxylate

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1,1-dimethylethyl 4-[[[1-(hydroxymethyl)-2-methoxy-2-oxoethyl]amino]carbonyl]-1-piperidinecarboxylate (i.e. the product of Example 7, Step A) (6.58 g, 19.92 mmol) in 70 mL of dry acetonitrile and 20 mL of dry dichloromethane was added triphenylphosphine (7.8 g, 29.87 mmol) and then 4.12 g (31.87 mmol) of N,N-diisopropylethylamine. The reaction mixture was stirred until homogeneous, and 4.59 g (29.87 mmol) of carbon tetrachloride 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 170 mL of ethyl acetate followed by 50 mL of saturated aqueous sodium bicarbonate solution. The mixture was stirred for 10 minutes, poured into 120 mL of water, and the organic layer was separated, washed with brine, dried over MgSO4 and concentrated under reduced pressure to give a yellow oil. The oil was purified by silica gel chromatography using 75-100% ethyl acetate in hexanes as eluant to give 2.95 g of the title compound as an oil containing traces of triphenylphosphine.

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
  8. customto give a yellow oil
  9. customThe oil was purified by silica gel chromatography

Sources & evidence

ORD record
ord-86f1c776ea914cc6a4daad58b3a1a85e
Source dataset
uspto-grants-2013_11
Patent number
US08586611B2

Reaction notes

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