Triethylamine → (S)-2-((1-(3-methylbutanoyl)piperidin-3-yl)methoxy)-6-nitrobenzonitrile

HRID 2280130Notes

Reaction equation

Cl.[N+:2]([C:5]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:14][C@H:15]2[CH2:20][CH2:19][CH2:18][NH:17][CH2:16]2)[C:6]=1[C:7]#[N:8])([O-:4])=[O:3].C(N(CC)CC)C.[C:28](Cl)(=[O:33])[CH2:29][CH:30]([CH3:32])[CH3:31]>C(Cl)Cl>[CH3:31][CH:30]([CH3:32])[CH2:29][C:28]([N:17]1[CH2:18][CH2:19][CH2:20][C@H:15]([CH2:14][O:13][C:9]2[CH:10]=[CH:11][CH:12]=[C:5]([N+:2]([O-:4])=[O:3])[C:6]=2[C:7]#[N:8])[CH2:16]1)=[O:33]

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of (S)-2-nitro-6-(piperidin-3-ylmethoxy)benzonitrile hydrochloride (Example 1d, 35.84 g, 120.41 mmol) in DCM (600 mL) cooled to 0° C. in an ice bath was added triethylamine (42 mL, 300.94 mmol) followed by dropwise addition of isovaleryl chloride (2.77 mL, 132.35 mmol). The reaction mixture was stirred under N2 for 30 minutes at 0° C., then at room temperature overnight. The solution was diluted with DCM and successively washed with 10% citric acid, saturated NaHCO3 solution, water, brine, dried over Na2SO4, filtered and concentrated to afford crude (S)-2-((1-(3-methylbutanoyl)piperidin-3-yl)methoxy)-6-nitrobenzonitrile as a golden brown oil (43.26 g). MS 346 (MH+). This material was used without purification in the next step.

Workup

customat room temperature
customovernight
washsuccessively washed with 10% citric acid, saturated NaHCO3 solution, water, brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-105d4bfc78ea437490002e451ee1a241
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09138013B2

Reaction notes

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