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

HRID 402556Notes

Reaction equation

HRID 402556 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>C(#N)C.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×

Procedure

A solution of 2-(3-(tert-butoxycarbonyl)phenyl)-3-methylpyridine-1-oxide (1 eq) and pyridine (4 eq) in acetonitrile (8 vol) was heated to 70° C. A solution of methanesulfonic anhydride (1.5 eq) in MeCN (2 vol) was added over 50 minutes via addition funnel while maintaining the temperature at less than 75° C. The mixture was stirred for an additional 0.5 hours after complete addition. The mixture was then allowed to cool to ambient temperature. Ethanolamine (10 eq) was added via addition funnel. After stirring for 2 hours, water (6 vol) was added, and the mixture was cooled to 10° C. After stirring for 3 hours, the solid was collected by filtration and washed with water (3 vol), 2:1 acetonitrile/water (3 vol), and acetonitrile (2×1.5 vol). The solid was dried to constant weight (less than 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. temperaturewhile maintaining the temperature at less than 75° C
  2. additionafter complete addition
  3. stirringAfter stirring for 2 hours
  4. temperaturethe mixture was cooled to 10° C
  5. stirringAfter stirring for 3 hours
  6. filtrationthe solid was collected by filtration
  7. washwashed with water (3 vol), 2:1 acetonitrile/water (3 vol), and acetonitrile (2×1.5 vol)
  8. dry with materialThe solid was dried to constant weight (less than 1% difference) in a vacuum oven at 50° C. with a slight N2

Sources & evidence

ORD record
ord-d44783e9e11f4facb530ae18f8aeca29
Source dataset
uspto-grants-2014_06
Patent number
US08742122B2

Reaction notes

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