Hydrochloric Acid → Ethyl 3-chloro-6-(pivalamidomethyl)picolinate

HRID 1469713Notes

Reaction equation

HRID 1469713 reaction equation
C(O[C:6]([NH:8][CH2:9][C:10]1[N:15]=[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:13]([Cl:21])=[CH:12][CH:11]=1)=[O:7])(C)(C)C.Cl.[C:23](Cl)(=O)[C:24](C)([CH3:26])[CH3:25]>CCOC(C)=O>[Cl:21][C:13]1[C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:15][C:10]([CH2:9][NH:8][C:6](=[O:7])[C:24]([CH3:26])([CH3:25])[CH3:23])=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 62493Pivaloyl chlorideHCID 86692224Ethyl 6-(((tert-butoxycarbonyl)amino)methyl)-3-chloropicolinate

Product 1

HCID 86692225Ethyl 3-chloro-6-(pivalamidomethyl)picolinateYield 89.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of ethyl 6-(((tert-butoxycarbonyl)amino)methyl)-3-chloropicolinate (100 mg, 0.318 mmol) in EtOAc saturated with HCl (1 mL) was stirred at rt for 1 h. The reaction mixture was concentrated and the concentrate was dissolved in CH2Cl2 (2 mL). The solution was treated with DIPEA (0.5 mL) followed by pivaloyl chloride (38 mg, 0.318 mmol) at 0° C. The reaction mixture was stirred at rt for 2 h. The reaction mixture was diluted with EtOAc and was washed with H2O and brine. The organic layer was separated, dried, filtered and concentrated to afford 85 mg of the title product. 1H NMR (300 MHz, DMSO-d6): δ 8.26 (br t, 1H), 8.04 (d, J=8.4 Hz, 1H), 7.35 (d, J=8.1 Hz, 1H), 4.40-4.31 (m, 4H), 1.33-1.10 (m, 12H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe concentrate was dissolved in CH2Cl2 (2 mL)
  3. additionThe solution was treated with DIPEA (0.5 mL)
  4. washwas washed with H2O and brine
  5. customThe organic layer was separated
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-0cae618dd96d423381c2b09bec0f53c4
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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