Ethanolamine → Benzoic acid, 3-(6-amino-3-methyl-2-pyridinyl)-, 1,1-dimethylethyl ester

HRID 716618Notes

Reaction equation

HRID 716618 reaction equation
[C:1]([O:5][C:6]([C:8]1[CH:9]=[C:10]([C:14]2[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N+:15]=2[O-])[CH:11]=[CH:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:22]1C=CC=CC=1.CS(OS(C)(=O)=O)(=O)=O.C(CN)O>CC#N.O>[C:1]([O:5][C:6](=[O:7])[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([C:14]2[C:19]([CH3:20])=[CH:18][CH:17]=[C:16]([NH2:22])[N:15]=2)[CH:9]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 700EthanolamineHCID 1049PyridineHCID 81560Methanesulfonic anhydrideHCID 584883712-(3-(Tert-butoxycarbonyl)phenyl)-3-methylpyridine 1-oxide

Product 1

HCID 45480517Benzoic acid, 3-(6-amino-3-methyl-2-pyridinyl)-, 1,1-dimethylethyl esterYield 53%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
10 °C

Procedure

A solution of 2-(3-(tert-butoxycarbonyl)phenyl)-3-methylpyridine-1-oxide (1 eq) and pyridine (4 eq) in MeCN (8 vol) is heated to 70° C. A solution of methanesulfonic anhydride (1.5 eq) in MeCN (2 vol) is added over 50 min via addition funnel maintaining the temperature at less than 75° C. The mixture is stirred for an additional 0.5 hours after complete addition. The mixture is then allowed to cool to ambient. Ethanolamine (10 eq) is added via addition funnel. After stirring for 2 hours, water (6 vol) is added and the mixture is cooled to 10° C. After stirring for NLT 3 hours, the solid is collected by filtration and washed with water (3 vol), 2:1 MeCN/water (3 vol), and MeCN (2×1.5 vol). The solid is dried to constant weight (<1% difference) in a vacuum oven at 50° C. with a slight N2 bleed to afford tert-butyl-3-(6-amino-3-methylpyridin-2-yl)benzoate as a red-yellow solid (53% yield).

Workup

  1. temperaturemaintaining the temperature at less than 75° C
  2. additionafter complete addition
  3. temperatureto cool to ambient
  4. stirringAfter stirring for 2 hours
  5. stirringAfter stirring for NLT 3 hours
  6. filtrationthe solid is collected by filtration
  7. washwashed with water (3 vol), 2:1 MeCN/water (3 vol), and MeCN (2×1.5 vol)
  8. dry with materialThe solid is dried to constant weight (<1% difference) in a vacuum oven at 50° C. with a slight N2

Sources & evidence

ORD record
ord-3698b297500f4be591d093a8118fb597
Source dataset
uspto-grants-2015_11
Patent number
US09192606B2

Reaction notes

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