tert-Butyl 4-oxopiperidine-1-carboxylate → HCID 67264921, compound

HRID 1685162Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:10]=[CH:11][N:12]([CH2:14][CH2:15][N:16]([CH3:18])[CH3:17])[CH:13]=2)[CH:5]=[CH:6][C:7]=1[F:8].C([Li])CCC.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][C:34](=[O:37])[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25]>C1COCC1>[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][C:34]([C:11]2[N:12]([CH2:14][CH2:15][N:16]([CH3:18])[CH3:17])[CH:13]=[C:9]([C:4]3[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=3)[N:10]=2)([OH:37])[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:25])[CH3:26]

Participants

Conditions

Temperature: -78 °C

Procedure

Dissolve {2-[4-(3-chloro-4-fluoro-phenyl)-imidazol-1-yl]-ethyl}-dimethylamine (1.00 equiv; 4.07 mmol; 1.09 g) in anhydrous THF (15 mL; 184.33 mmol) and cool the mixture to −78° C. Slowly add n-butyl lithium (1.40 equiv; 5.70 mmol; 3.56 mL) (1.6M Aldrich), and stir at −78° C. for 30 min, then add a THF (10 mL) solution of N-t-butoxycarbonyl-4-piperidone (1.20 equiv; 4.89 mmol; 973.43 mg) dropwise over 10 min. After 20 min, warm the reaction to RT and stir 3 h. Partition between EA and water. Wash the organic layer with brine, NaCl aq (50/50) and dry over MgSO4. Filter and concentrate. Purify the residue by ISCO chromatography over a Biotage 40M column eluting with 100% DCM to 10% MeOH/DCM to give 785 mg (41%) of the title compound as a white solid. ES(MS): (m/z)=467.0 (M+H).

Workup

temperaturewarm
customthe reaction to RT
customPartition between EA and water
washWash the organic layer with brine, NaCl aq (50/50)
dry with materialdry over MgSO4
filtrationFilter
concentrationconcentrate
customPurify the residue by ISCO chromatography over a Biotage 40M column
washeluting with 100% DCM to 10% MeOH/DCM

Sources & evidence

ORD record: ord-a8fca0ba385340f0b71c272636101591
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08148387B2

Reaction notes

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