Tetrahydrofuran → 2-(2-Tert-butoxycarbonylamino-4-pyridyl)-1-(3-methylphenyl)ethanone

HRID 1268725Notes

Reaction equation

HRID 1268725 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[C:13]([CH3:15])[CH:12]=[CH:11][N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:16]([Li])CCC.[CH3:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26].[O:27]1CCC[CH2:28]1>[Cl-].[Na+].O>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[C:13]([CH2:15][C:28]([C:23]2[CH:22]=[CH:21][CH:26]=[C:25]([CH3:16])[CH:24]=2)=[O:27])[CH:12]=[CH:11][N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 8058HexaneHCID 11063648tert-butyl N-(4-methylpyridin-2-yl)carbamateHCID 178418339Butyllithium

Product 1

HCID 116168302-(2-Tert-butoxycarbonylamino-4-pyridyl)-1-(3-methylphenyl)ethanoneYield 81%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 2-tert-butoxycarbonylamino-4-methylpyridine (146 g, 0.700 mol) in anhydrous tetrahydrofuran (1.30 L) was cooled to −78° C. and, with stirring, a solution of 1.6 M n-butyl lithium in hexane (875 mL, 1.40 mol) was added dropwise. After the completion of the dropwise addition, the mixture was stirred at 0° C. for 30 min. and cooled to −78° C. A solution of N-(3-methylbenzoyl)propyleneimine (123 g, 0.700 mol) in anhydrous tetrahydrofuran (130 mL) was added dropwise. After the completion of the dropwise addition, the mixture was stirred at −78° C. for 1 hr., warmed to room temperature and stirred for 1 hr. Saturated brine (1.30 L) was added to the reaction mixture and the organic layer was separated. The aqueous layer was extracted with ethyl acetate and the combined organic layer was dried and concentrated. The crude crystals were recrystallized from ethyl acetate to give the title compound (185 g, yield 81%).

Workup

  1. additionAfter the completion of the dropwise addition
  2. stirringthe mixture was stirred at 0° C. for 30 min.
  3. additionAfter the completion of the dropwise addition
  4. stirringthe mixture was stirred at −78° C. for 1 hr
  5. temperature, warmed to room temperature
  6. stirringstirred for 1 hr
  7. customthe organic layer was separated
  8. extractionThe aqueous layer was extracted with ethyl acetate
  9. customthe combined organic layer was dried
  10. concentrationconcentrated
  11. customThe crude crystals were recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-2a81db360cde4ab8986d9e3eb91c6748
Source dataset
uspto-grants-2007_04
Patent number
US07199124B2

Reaction notes

Loading…