Water → (R)-tert-butyl 2-((2-carbamoylpyridin-3-yloxy)methyl)pyrrolidine-1-carboxylate

HRID 2406777Notes

Reaction equation

[C:1]([C:3]1[C:8]([O:9][CH2:10][C@H:11]2[CH2:15][CH2:14][CH2:13][N:12]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:7][CH:6]=[CH:5][N:4]=1)#[N:2].[OH-:23].[K+].O>C(O)(C)(C)C>[C:1]([C:3]1[C:8]([O:9][CH2:10][C@H:11]2[CH2:15][CH2:14][CH2:13][N:12]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:7][CH:6]=[CH:5][N:4]=1)(=[O:23])[NH2:2]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of (R)-tert-butyl 2-((2-cyanopyridin-3-yloxy)methyl)pyrrolidine-1-carboxylate (3.62 g, 11.9 mmol, EXAMPLE 1 Step 1) in tert-butanol (110 mL) was added potassium hydroxide pellet (10.0 g, 179 mmol) at room temperature. The resulting mixture was stirred at 80° C. for 0.5 h. After cooling to room temperature, the mixture was poured into water, and the aqueous layer was extracted with ethyl acetate twice. The combined organic layers were washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The residual oil was purified by silica gel column chromatography (dichloromethane to methanol/dichloromethane 1:15) to give 3.43 g (90%) of the title compound as a white amorphous powder.

Workup

temperatureAfter cooling to room temperature
extractionthe aqueous layer was extracted with ethyl acetate twice
washThe combined organic layers were washed with brine
dry with materialdried over magnesium sulfate
concentrationconcentrated in vacuo
customThe residual oil was purified by silica gel column chromatography (dichloromethane to methanol/dichloromethane 1:15)

Sources & evidence

ORD record: ord-1d1a77fe201d43f78a4187ad1dfe18fd
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809380B2

Reaction notes

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