tert-Butyl 4-(2-oxoethyl)piperidine-1-carboxylate → 4-(2-Hydroxy-2-oxazolo[4,5-c]pyridin-2-ylethyl)piperidine-1-carboxylic acid tert-butyl ester

HRID 217165Notes

Reaction equation

C([Mg]Cl)(C)C.[O:6]1[C:14]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:8]=[CH:7]1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([CH2:28][CH:29]=[O:30])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>C1COCC1>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([CH2:28][CH:29]([OH:30])[C:7]2[O:6][C:14]3[CH:13]=[CH:12][N:11]=[CH:10][C:9]=3[N:8]=2)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]

Participants

Conditions

Temperature: 20 °C

Procedure

i-PrMgCl (0.44 mL of a 2 mmol/mL solution in THF, 0.88 mmol) was added dropwise to a stirred solution of oxazolo[4,5-c]pyridine (105 mg, 0.87 mmol) in anhydrous THF (3 mL) at 0° C. After 1 h, a solution of 4-(2-oxo-ethyl)piperidine-1-carboxylic acid tert-butyl ester (198 mg, 0.87 mmol) in anhydrous THF (2 mL) was added, then the mixture was allowed to warm to 20° C. over 16 h, before being quenched with saturated aqueous NH4Cl (10 mL). The layers were separated, then the aqueous phase was extracted with EtOAc (3×15 mL). The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo. Flash chromatography (EtOAc) of the residue furnished the title compound: m/z (ES+)=348.1 [M+H]+.

Workup

custombefore being quenched with saturated aqueous NH4Cl (10 mL)
customThe layers were separated
extractionthe aqueous phase was extracted with EtOAc (3×15 mL)
dry with materialThe combined organic extracts were dried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-44f56a748eb04822bd8f1f6495fdbf2b
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08193359B2

Reaction notes

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