3-Hydroxypyridine → tert-Butyl 3-(pyridin-3-yloxy)pyrrolidine-1-carboxylate

HRID 2171995Notes

Reaction equation

[OH:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.O[C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[N:17]1[CH:18]=[CH:19][CH:20]=[C:15]([O:1][CH:2]2[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]2)[CH:16]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of tert-butyl 3-hydroxypyrrolidine-1-carboxylate (500 mg, 2.67 mmol) in anhydrous THF (13 mL) under nitrogen were added 3-hydroxypyridine (508 mg, 5.34 mmol) and triphenylphosphine (1.40 g, 5.34 mmol). The reaction mixture was cooled to 0° C. and DEAD (775 μL, 4.27 mmol) was added dropwise. The solution was allowed to warm to room temperature and stirred overnight. The reaction mixture was concentrated under reduced pressure then diluted with dichloromethane and filtered. The filtrate was washed three times with NaOH 0.2N, dried over Na2SO4 then concentrated. The residue was purified on column chromatography (eluent: pentane/acetone 9/1 to 7/3) to give the title compound (606 mg, 86%) as a wax.

Workup

temperatureto warm to room temperature
concentrationThe reaction mixture was concentrated under reduced pressure
additionthen diluted with dichloromethane
filtrationfiltered
washThe filtrate was washed three times with NaOH 0.2N
dry with materialdried over Na2SO4
concentrationthen concentrated
customThe residue was purified on column chromatography (eluent: pentane/acetone 9/1 to 7/3)

Sources & evidence

ORD record: ord-f889bcd894cc4a678994339dca59b9cb
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09051321B2

Reaction notes

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