2-Amino-1-butanol, (+)- → 2-(4-Chloro-2,6-dimethyl-phenoxy)-4-(1-hydroxymethyl-propylamino)-6-methyl-nicotinic acid methyl ester

HRID 1831659Notes

Reaction equation

HRID 1831659 reaction equation
[CH3:1][O:2][C:3](=[O:22])[C:4]1[C:9](Cl)=[CH:8][C:7]([CH3:11])=[N:6][C:5]=1[O:12][C:13]1[C:18]([CH3:19])=[CH:17][C:16]([Cl:20])=[CH:15][C:14]=1[CH3:21].[NH2:23][C@@H:24]([CH2:27][CH3:28])[CH2:25][OH:26]>CN1CCCC1=O.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:22])[C:4]1[C:9]([NH:23][CH:24]([CH2:25][OH:26])[CH2:27][CH3:28])=[CH:8][C:7]([CH3:11])=[N:6][C:5]=1[O:12][C:13]1[C:18]([CH3:19])=[CH:17][C:16]([Cl:20])=[CH:15][C:14]=1[CH3:21]

Participants

5

Reactant 2

HCID 1200842-Amino-1-butanol, (+)-HCID 248062602-(4-Chloro-2,6-dimethyl-phenoxy)-4-chloro-6-methyl-nicotinic acid methyl ester

Product 1

HCID 101786472-(4-Chloro-2,6-dimethyl-phenoxy)-4-(1-hydroxymethyl-propylamino)-6-methyl-nicotinic acid methyl esterYield 64%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 4-chloro-2-(4-chloro-2,6-dimethyl-phenoxy)-6-methyl-nicotinic acid methyl ester (9.000 g, 26.45 mmol) and (S)-2-amino-1-butanol (12.7 ml) in 1-methyl-2-pyrrolidinone was heated at 130° C. for 2 hr, then at 100° C. overnight. The mixture cooled to rt and poured into ice-water and diluted with ethyl acetate. The organic layer was separated, washed with water, dried over anhydrous sodium sulfate, filtered, and concentrated to dryness to give 13.6 g of crude product as a light yellow oil. The oil was purified through silica gel column chromatography using chloroform to 2% MeOH in chloroform as eluent to give 6.6839 g (64%) of the title compound as a white glass foam. The glass foam was triturated with hexane to give a white solid. The solid was recrystallized from di-iso-propyl ether to give a white crystals, mp 122.5–124° C. Anal. calc. for C20H25CIN2O4: C, 61.14; H, 6.41; N, 7.13; found: C, 60.98; H, 6.43; N, 6.95.

Workup

  1. customat 100° C.
  2. customovernight
  3. temperatureThe mixture cooled to rt
  4. customThe organic layer was separated
  5. washwashed with water
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customto give 13.6 g of crude product as a light yellow oil
  10. customThe oil was purified through silica gel column chromatography

Sources & evidence

ORD record
ord-cee5dd78604d477f8b3c624337cf1e26
Source dataset
uspto-grants-2006_06
Patent number
US07067664B1

Reaction notes

Loading…