P,P-Diphenylphosphinic azide → tert-Butyl (2-chloro-5-fluoro-6-methoxypyridin-3-yl)carbamate

HRID 15129

Reaction equation

HRID 15129 reaction equation
[Cl:1][C:2]1[C:7](C(O)=O)=[CH:6][C:5]([F:11])=[C:4]([O:12][CH3:13])[N:3]=1.C1(P([N:28]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.[C:31](=[O:34])(O)[O-:32].[Na+].[C:36]1([CH3:42])[CH:41]=CC=C[CH:37]=1.C(N(CC)CC)C.C(O)(C)(C)C>>[Cl:1][C:2]1[C:7]([NH:28][C:31](=[O:34])[O:32][C:36]([CH3:42])([CH3:41])[CH3:37])=[CH:6][C:5]([F:11])=[C:4]([O:12][CH3:13])[N:3]=1

Participants

5

Reactant 4

HCID 199401P,P-Diphenylphosphinic azideHCID 516892Sodium BicarbonateHCID 455882302-Chloro-5-fluoro-6-methoxynicotinic acidHCID 86614145Toluene triethylamine tert-butanol

Product 1

HCID 71463986tert-Butyl (2-chloro-5-fluoro-6-methoxypyridin-3-yl)carbamate

Conditions

Temperature
100 °C

Procedure

A mixture of 2-chloro-5-fluoro-6-(methyloxy)-3-pyridinecarboxylic acid (32.65 g, 159 mmol) in toluene/triethylamine/tert-butanol (300 ml/26.4 ml/75 ml) was treated with diphenylphosphoryl azide (37.7 ml, 174.8 mmol) and heated to 100° C. for 2 hours. The mixture was treated with saturated aqueous sodium bicarbonate solution (500 ml) then extracted with ethyl acetate (3×500 ml). The combined organic extracts were dried over magnesium sulphate and evaporated. The residue was chromatographed eluting with 0-40% dichloromethane in petrol affording the product as a white solid (36.35 g, 83%).

Workup

  1. extractionthen extracted with ethyl acetate (3×500 ml)
  2. dry with materialThe combined organic extracts were dried over magnesium sulphate
  3. customevaporated
  4. customThe residue was chromatographed
  5. washeluting with 0-40% dichloromethane in petrol affording the product as a white solid (36.35 g, 83%)

Sources & evidence

ORD record
ord-186390d6ffe74cdbb70148554e5003f6
Source dataset
uspto-grants-2010_06
Patent number
US07732460B2

Linked notes

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