Sodium hydride → HCID 86720990, compound

HRID 524932Notes

Reaction equation

[H-].[Na+].[OH:3][C@H:4]1[CH2:9][CH2:8][CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5]1.Cl[C:18]1[CH:23]=[CH:22][N:21]=[CH:20][C:19]=1[N+:24]([O-:26])=[O:25]>C1COCC1>[N+:24]([C:19]1[CH:20]=[N:21][CH:22]=[CH:23][C:18]=1[O:3][C@H:4]1[CH2:9][CH2:8][CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5]1)([O-:26])=[O:25]

Participants

Conditions

Temperature: 0 °C

Procedure

Sodium hydride (492.0 mg, 12.30 mmol) was added to a solution of tert-butyl (3S)-3-hydroxypiperidine-1-carboxylate (2.095 g, 10.41 mmol) in THF (20 mL) and the reaction stirred at 0° C. for 15 minutes. A suspension of 4-chloro-3-nitro-pyridine (1.5 g, 9.461 mmol) in THF (10 mL) was added and the reaction allowed to warm slowly to ambient temperature over 2 hours. The reaction was quenched with water and the mixture was partitioned between EtOAc and brine. The combined organic extract was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion, 80 g column, eluting with 0 to 100% EtOAc/Petroleum Ether) to give tert-butyl (3S)-3-[(3-nitro-4-pyridyl)oxy]piperidine-1-carboxylate as a pale yellow solid (2.65 g, 87% Yield, 93% ee). MS (ES+) 324.1.

Workup

additionwas added
temperatureto warm slowly to ambient temperature over 2 hours
customThe reaction was quenched with water
customthe mixture was partitioned between EtOAc and brine
extractionThe combined organic extract
washwas washed with brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography (ISCO Companion, 80 g column, eluting with 0 to 100% EtOAc/Petroleum Ether)

Sources & evidence

ORD record: ord-4780ed625eb8453e9e6b6fbefcaac2c6
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340546B2

Reaction notes

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