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

HRID 2043733Notes

Reaction equation

[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([C:18]2[O:19][CH2:20][CH:21]([C:23]([O:25][CH3:26])=[O:24])[N:22]=2)[CH2:14][CH2:13]1)=[O:11].N12CCCN=C1CCCCC2.BrC(Cl)(Cl)Cl>ClCCl>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([C:18]2[O:19][CH:20]=[C:21]([C:23]([O:25][CH3:26])=[O:24])[N:22]=2)[CH2:14][CH2:13]1)=[O:11]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of methyl 2-[1-[(2,5-dimethylphenyl)acetyl]-4-piperidinyl]-4,5-dihydro-4-oxazolecarboxylate (i.e. the product of Example 9, Step D) (1.09 g, 3.04 mmol) in 25 mL of dichloromethane at 0° C. was added 1,8-diazabicyclo[5.4.0]undec-7-ene (508 mg, 3.34 mmol). Bromotrichloromethane (662 mg, 3.34 mmol) was then added dropwise over 5 minutes. The reaction mixture was stirred for 6 h at 0° C. The reaction mixture was washed with saturated aqueous ammonium chloride (2×50 mL), the aqueous phase was back-extracted with ethyl acetate (2×25 mL), and the combined organic layers were dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography using 50-100% of ethyl acetate in hexanes as eluant to give 600 mg of the title compound as an oil.

Workup

washThe reaction mixture was washed with saturated aqueous ammonium chloride (2×50 mL)
extractionthe aqueous phase was back-extracted with ethyl acetate (2×25 mL)
dry with materialthe combined organic layers were dried over MgSO4
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record: ord-9f75c0cc64cd4363ba480b6d7d21a7e6
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08586611B2

Reaction notes

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