tert-Butyl 4-formylpiperidine-1-carboxylate → HCID 118005515, compound

HRID 1478496Notes

Reaction equation

C([Mg]Cl)(C)C.Br[C:7]1[CH:8]=[CH:9][C:10]([C:13]([F:16])([F:15])[F:14])=[N:11][CH:12]=1.[CH:17]([CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1)=[O:18]>C1COCC1>[OH:18][CH:17]([C:7]1[CH:12]=[N:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=1)[CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]1

Participants

Conditions

Temperature: 10 °C

Procedure

A solution of isopropylmagnesium chloride (2.0 M in THF, 40.3 mL, 80.6 mmol) was added dropwise by syringe to a solution of 5-bromo-2-(trifluoromethyl)pyridine (19.5 g, 86.3 mmol) in dry THF (12 mL) at 2° C. After 30 minutes, tert-butyl 4-formylpiperidine-1-carboxylate (12.3 g, 57.3 mmol) was added to the Grignard solution at 2° C. as a solid. The reaction mixture was warmed to 10° C. over 1.5 hours after which it was quenched with saturated aqueous ammonium chloride solution. The mixture was partitioned between water and ethyl acetate. The separated aqueous phase was further extracted with ethyl acetate and washed with saturated aqueous NaCl solution. The organic phase was dried (MgSO4), filtered, and concentrated and used crude in the next step.

Workup

customwas quenched with saturated aqueous ammonium chloride solution
customThe mixture was partitioned between water and ethyl acetate
extractionThe separated aqueous phase was further extracted with ethyl acetate
washwashed with saturated aqueous NaCl solution
dry with materialThe organic phase was dried (MgSO4)
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-7bc9618d05d94253b8d8a42bfb424575
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09403816B2

Reaction notes

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