Ammonium Chloride → HCID 59331940, compound

HRID 1798404Notes

Reaction equation

HRID 1798404 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]Br)=[CH:4][C:3]=1[F:10].[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].[Cl-].[NH4+]>>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][C:21]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([F:10])[CH:4]=2)([OH:24])[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

4

Reactant 3

HCID 25517Ammonium ChlorideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178505943HCID 178505943, compound

Product 1

HCID 59331940HCID 59331940, compoundYield 30.4%

Procedure

A solution of 4-chloro-3-fluorophenylmagnesium bromide (15 ml, 7.5 mmol, 0.5M in THF) was added, under nitrogen, to 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (1.02 g, 5.1 mmol). After 24 hours, saturated ammonium chloride solution was added then the organic solvent was removed in vacuo. The mixture was extracted with ethyl acetate, then this extract was washed with brine, dried (MgSO4), filtered and concentrated to afford a residue which was purified by column chromatography (SiO2), eluting with gradient of ethyl acetate/petrol (0% to 20%) to afford the title compound (511 mg, 30%). 1H NMR (Me-d3-OD) δ 1.48 (9H, s), 1.67 (2H, br.d), 1.92 (2H, td), 3.16-3.29 (2H, m), 3.99 (2H, br.d), 7.27 (1H, dd), 7.38 (1H, dd), 7.42 (1H, t).

Workup

  1. customthe organic solvent was removed in vacuo
  2. extractionThe mixture was extracted with ethyl acetate
  3. washthis extract was washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a residue which
  8. customwas purified by column chromatography (SiO2)
  9. washeluting with gradient of ethyl acetate/petrol (0% to 20%)

Sources & evidence

ORD record
ord-27043d89398245ed8b60b5360a7ff19e
Source dataset
uspto-grants-2013_01
Patent number
US08343953B2

Reaction notes

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