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

HRID 1039135Notes

Reaction equation

HRID 1039135 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×

Conditions

Temperature
10 °C

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 min 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. 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 (<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. temperatureto cool to ambient
  4. stirringAfter stirring for 2 hours
  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 (<1% difference) in a vacuum oven at 50° C. with a slight N2

Sources & evidence

ORD record
ord-cee75a7753c943a98b96e4dbd37f7bc2
Source dataset
uspto-grants-2013_10
Patent number
US08552034B2

Reaction notes

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