Carbon Dioxide → {6-[(tert-Butoxycarbonyl)amino]pyridin-2-yl}acetic acid

HRID 1454817Notes

Reaction equation

HRID 1454817 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[N:9]=1)([CH3:4])([CH3:3])[CH3:2].C([N-]C(C)C)(C)C.[Li+].[C:24](=[O:26])=[O:25]>C1COCC1.C1COCC1.CCCCCCC.C(C1C=CC=CC=1)C>[C:1]([O:5][C:6]([NH:7][C:8]1[N:9]=[C:10]([CH2:14][C:24]([OH:26])=[O:25])[CH:11]=[CH:12][CH:13]=1)=[O:15])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 280Carbon DioxideHCID 2724682Lithium diisopropylamideHCID 11367776tert-Butyl (6-methylpyridin-2-yl)carbamate

Product 1

HCID 53401509{6-[(tert-Butoxycarbonyl)amino]pyridin-2-yl}acetic acid

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 22742125Tetrahydrofuran heptane ethylbenzolSolvent

Conditions

Temperature
-20 °C

Procedure

(6-Methyl-pyridin-2-yl)-carbamic acid tert-butyl ester (1.04 g, Pitts, J. Med. Chem., 43, 2000, 27) under an argon atmosphere in THF (40 mL) was cooled to −20° C. and treated dropwise at −20° C. with 5.5 mL of a 2 M solution of lithium diisopropylamide in THF/heptane/ethylbenzene (Fluka). The solution was stirred 1 h at −20° C., cooled to −70° C. and then treated with an access of dry ice. The mixture was allowed to warm to 10° C. and partitioned between aqueous 1N HCl and AcOEt, the layers were separated, the organic layer dried over Na2SO4, filtered, evaporated and the residue was purified by flash chromatography (MeOH/CH2Cl2 0-15%). The obtained material was triturated with ether, the crystalline solid obtained was filtered off by suction and dried in vacuo to give (6-tert-butoxycarbonylamino-pyridin-2-yl)-acetic acid as an off-white solid (0.3 g). MS (ESI−): 251.1 ([M−H]−).

Workup

  1. temperaturecooled to −70° C.
  2. temperatureto warm to 10° C.
  3. custompartitioned between aqueous 1N HCl and AcOEt
  4. customthe layers were separated
  5. dry with materialthe organic layer dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customthe residue was purified by flash chromatography (MeOH/CH2Cl2 0-15%)
  9. customThe obtained material was triturated with ether
  10. customthe crystalline solid obtained
  11. filtrationwas filtered off by suction
  12. customdried in vacuo

Sources & evidence

ORD record
ord-d56c9106e93b456e9288c999be43e516
Source dataset
uspto-grants-2009_01
Patent number
US07482341B2

Reaction notes

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