tert-Butanol → 3-N-Boc-aMino-2-chloro-5-fluoropyridine

HRID 707243Notes

Reaction equation

[Cl:1][C:2]1[N:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=1C(O)=O.[C:12]([OH:16])([CH3:15])([CH3:14])[CH3:13].C([N:19]([CH2:22]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:31])C=CC=CC=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:3]([NH:19][C:22](=[O:31])[O:16][C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:7][C:8]([F:11])=[CH:9][N:10]=1

Participants

Conditions

Temperature: 90 °C

Procedure

2-Chloro-5-fluoronicotinic acid (7.03 g, 40.0 mmol) was dissolved in a mixture of toluene (100 mL), tert-butanol (20 ml, 209 mmol), and triethylamine (6.8 ml, 48.9 mmol). Diphenylphosphoryl azide (9 ml, 41.8 mmol) was added slowly and the reaction heated at 90° C. After 2 hours the reaction was cooled and concentrated under reduced pressure. The residue was partitioned between water (100 mL), saturated sodium bicarbonate (70 mL) and ethyl acetate (300 mL). The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (hexane to ethyl acetate gradient) gave the desired tert-butyl (2-chloro-5-fluoropyridin-3-yl)carbamate (4.97 g, 20.15 mmol, 50.3% yield) as a thick oil.

Workup

temperatureAfter 2 hours the reaction was cooled
concentrationconcentrated under reduced pressure
customThe residue was partitioned between water (100 mL), saturated sodium bicarbonate (70 mL) and ethyl acetate (300 mL)
dry with materialThe organic was dried with magnesium sulfate
customevaporated to dryness under reduced pressure
customPurification

Sources & evidence

ORD record: ord-867fb28882444f0fb83d5d50de0927a0
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174992B2

Reaction notes

Loading…