Hydrochloric Acid → tert-Butyl 5-((tert-butoxycarbonyl)amino)picolinate

HRID 354341Notes

Reaction equation

HRID 354341 reaction equation
[C:1]([O:5][C:6]([C:8]1[CH:16]=[CH:15][C:11](C(O)=O)=[CH:10][N:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:19]([CH2:22]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:31])C=CC=CC=1.Cl.[C:42]([OH:46])([CH3:45])([CH3:44])[CH3:43]>C1(C)C=CC=CC=1>[C:42]([O:46][C:22]([NH:19][C:11]1[CH:15]=[CH:16][C:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[N:9][CH:10]=1)=[O:31])([CH3:45])([CH3:44])[CH3:43]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 222714476-[(Tert-butoxy)carbonyl]pyridine-3-carboxylic acid

Product 1

HCID 23512171tert-Butyl 5-((tert-butoxycarbonyl)amino)picolinateYield 76%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a stirred mixture of 6-tert-butoxycarbonylnicotinic acid (1.9 g, 8.51 mmol) and triethylamine (1.17 g, 11.49 mmol) in tert-BuOH (30 ml) and toluene (30 ml) was added a solution of diphenyl phosphoryl azide (2.93 g, 10.64 mmol) in toluene (3 ml) at room temperature. The resulting mixture was then heated at reflux for 5 hr. After cooling, ice and 1N HCl (5 ml) was added to the mixture and extracted with toluene. The extracts were washed with brine, dried over Na2SO4, and evaporated. The residue was chromatographed on silica gel (50 ml) with toluene-EtOAc (5:1, v/v) as eluent to give tert-butyl 5-tert-butoxycarbonylamino-2-pyridinecarboxylate (1.9 g, 76%) as a gum. 1H-NMR (CDCl3) δ1.53 (s, 9 H), 1.63 (s, 9 H), 6.82 (br s, 1 H), 8.01 (d, J=8.8 Hz, 1 H), 8.17 (m, 1 H), 8.46 (d, J=2.4 Hz, 1 H).

Workup

  1. temperatureThe resulting mixture was then heated
  2. temperatureat reflux for 5 hr
  3. temperatureAfter cooling
  4. extractionextracted with toluene
  5. washThe extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customThe residue was chromatographed on silica gel (50 ml) with toluene-EtOAc (5:1

Sources & evidence

ORD record
ord-8e0f474dfda54faa9791dd67fd7fa0b4
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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