Hydrochloric Acid → 6-Chloro-5-(1-fluorocyclobutyl)pyridine-2-carboxylic acid

HRID 624995Notes

Reaction equation

P([O-])([O-])([O-])=O.[Cl:6][C:7]1[N:12]=[C:11]([CH2:13][OH:14])[CH:10]=[CH:9][C:8]=1[C:15]1([F:19])[CH2:18][CH2:17][CH2:16]1.Cl([O-])=[O:21].[Na+].Cl[O-].[Na+].[OH-].[Na+].Cl>C(#N)C.O.CC1(C)N([O])C(C)(C)CCC1>[Cl:6][C:7]1[N:12]=[C:11]([C:13]([OH:21])=[O:14])[CH:10]=[CH:9][C:8]=1[C:15]1([F:19])[CH2:18][CH2:17][CH2:16]1

Participants

Conditions

Temperature: 35 °C

Procedure

Aqueous phosphate buffer (pH=6.7, 0.7 mL) and TEMPO (2.54 mg, 16.2 μmol) were added to a solution of (6-chloro-5-(1-fluorocyclobutyl)pyridin-2-yl)methanol (Example 130 d, 50 mg, 232 μmol) in acetonitrile (1 mL) under an argon atmosphere. The reaction mixture was warmed to 35° C. A solution of sodium chlorite (52.4 mg, 464 μmol) in 150 μL water and a solution of sodium hypochlorite (2.66 mg, 2.19 μL, 4.64 μmol) in 100 μL water were added simultaneously over a period of 30 min. Stirring was continued at 35° C. for 20 h. Water (40 mL) and 2 N NaOH solution (8 mL) were added. The mixture was poured into an ice cold Na2SO3 solution (1.62 Na2SO3 g in 30 mL water) and stirred for 30 min. at ambient temperature. Under ice cooling the mixture was acidified with 25 mL 2 N HCl solution and extracted with a mixture of 100 mL EtOAc and 20 mL THF. The organic layer was dried over Na2SO4, filtered and the solvent concentrated in vacuo to give the title compound (66 mg, 90%) as yellow oil, MS(ESI): m/e=230.4 [MH+].

Workup

stirringstirred for 30 min. at ambient temperature
extractionextracted with a mixture of 100 mL EtOAc and 20 mL THF
dry with materialThe organic layer was dried over Na2SO4
filtrationfiltered
concentrationthe solvent concentrated in vacuo

Sources & evidence

ORD record: ord-143d601014d34a4c813e4599ead6a98a
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09303012B2

Reaction notes

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