Tributylphosphine → (S)-tert-butyl-4-(3-(6-bromopyridin-3-yloxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

HRID 407946Notes

Reaction equation

[Br:1][C:2]1[N:7]=[CH:6][C:5]([O:8][C@@H:9]([CH2:26][CH2:27]O)[C:10]([NH:12][CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)=[O:11])=[CH:4][CH:3]=1.C(P(CCCC)CCCC)CCC.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C1(C)C=CC=CC=1>[C:22]([O:21][C:19]([N:16]1[CH2:15][CH2:14][CH:13]([N:12]2[CH2:27][CH2:26][C@H:9]([O:8][C:5]3[CH:6]=[N:7][C:2]([Br:1])=[CH:3][CH:4]=3)[C:10]2=[O:11])[CH2:18][CH2:17]1)=[O:20])([CH3:23])([CH3:25])[CH3:24]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of (S)-tert-butyl 4-(2-(6-bromopyridin-3-yloxy)-4-hydroxybutanamido)piperidine-1-carboxylate (1.30 g, 2.84 mmol) and tributylphosphine (689 mg, 3.40 mmol) in toluene (15 mL) was degassed with nitrogen bubble for 10 minutes and then cooled to 0° C. Di-tert-butyl diazene-1,2-dicarboxylate (784 mg, 3.4 mmol) dissolved in toluene (5 mL) and was added over a 5 minute period. The reaction was allowed to warm to ambient temperature over 12 hours. The reaction was concentrated in vacuo and purified by silica gel chromatography eluting with 1:1 hexanes/EtOAc to yield (S)-tert-butyl-4-(3-(6-bromopyridin-3-yloxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (934 mg, 75%) as an off-white solid.

Workup

custombubble for 10 minutes
additionwas added over a 5 minute period
temperatureto warm to ambient temperature over 12 hours
concentrationThe reaction was concentrated in vacuo
custompurified by silica gel chromatography
washeluting with 1:1 hexanes/EtOAc

Sources & evidence

ORD record: ord-1a5a7ba856064159b7e07e86e4436b88
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754226B2

Reaction notes

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