Water → 3-(2-(3-Chlorophenyl)ethyl)-N-(1,1-dimethylethyl)-2-pyridinecarboxamide

HRID 1606944Notes

Reaction equation

HRID 1606944 reaction equation
[CH3:1][C:2]([NH:5][C:6]([C:8]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][N:9]=1)=[O:7])([CH3:4])[CH3:3].C([Li])CCC.[Cl:20][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=1)[CH2:24]Cl.O>O1CCCC1.[Br-].[Na+].C(OCC)(=O)C>[Cl:20][C:21]1[CH:22]=[C:23]([CH2:24][CH2:14][C:13]2[C:8]([C:6]([NH:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])=[N:9][CH:10]=[CH:11][CH:12]=2)[CH:26]=[CH:27][CH:28]=1

Participants

8

Reactant 4

HCID 962WaterHCID 12103m,alpha-DichlorotolueneHCID 5463796N-tert-Butyl-3-methylpyridine-2-carboxamideHCID 178418339Butyllithium

Product 1

HCID 141286953-(2-(3-Chlorophenyl)ethyl)-N-(1,1-dimethylethyl)-2-pyridinecarboxamideYield 105.7%

Reagents, catalysts & solvents 3

HCID 253881Sodium BromideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-40 °C

Procedure

To a cold (-40° C.) solution of N-(1,1-dimethylethyl)-3-methyl-2-pyridinecarboxamide (31.5 g; 0.16 mol) in 600 mL of dry tetrahydrofuran was added n-butyllithium in hexanes (2.5 mol; 131 mL) while the temperature was maintained at -40° C. The solution turned deep red after one equivalent was added. Sodium bromide (1.6 g) was added and the mixture was stirred for 10 min. A solution of m-chlorobenzyl-chloride (26.5 g; 0.174 mol) in 125 mL of dry tetrahydrofuran (THF) was added while the temperature was again maintained at -40° C. The reaction mixture was stirred for a further 30 min. after which water was carefully added until the color dissipated. The product was isolated by extraction into ethyl acetate which was washed with water, dried (MgSO4) and concentrated to give 53.6 g (HPLC purity 89%; yield 92%) of 3-[2-(3-chlorophenyl)ethyl]-N-(1,1-dimethylethyl)-2-pyridine carboxamide as an oil. This oil may be used directly in the next step or crystallized from hexanes to give 3-[2-(3-chlorophenyl)ethyl]-N-(1,1-dimethylethyl)-2-pyridine carboxamide as a white solid: m.p. 45°-46° C.; NMR (200 MHz,CDCl3)δ1.50 (s,9H), 2.96 (t,2H,J=8 Hz); 3.40 (t,2H,J=8 Hz); 7.0-7.3 (m,5H); 7.39 (dd,1H,J=8, 2 Hz); 7.98 (br s, 1H); 8.30 (dd,1H, J=4, 1 Hz); mass spectrum, m/e (rel intensity) 316M+ (19). Anal. Calcd for C18H21N2OCl: C,68.22; H,6.68; N,8.88; Cl,11.19. Found: C,68.25; H,6.59; N,8.78; Cl,11.10.

Workup

  1. additionwas added
  2. temperaturewas again maintained at -40° C
  3. additionwas carefully added until the color
  4. washwas washed with water
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-23d0dfb946ce4ccdb146bf87b04826d1
Source dataset
uspto-grants-1989_09
Patent number
US04863931

Reaction notes

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