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

HRID 906659Notes

Reaction equation

HRID 906659 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.CC1C=CC(S(Cl)(=O)=O)=CC=1.NCCO>C(#N)C>[NH2:22][C:16]1[N:15]=[C:14]([C:10]2[CH:9]=[C:8]([CH:13]=[CH:12][CH:11]=2)[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:19]([CH3:20])=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 700EthanolamineHCID 1049PyridineHCID 73974-Toluenesulfonyl chlorideHCID 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 51.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

2-(3-(tert-Butoxycarbonyl)phenyl)-3-methylpyridine 1-oxide (29.8 g, 104 mmol) was dissolved in a mixture of acetonitrile (662 mL) and pyridine (33.8 mL, 418 mmol) under an atmosphere of argon. 4-Methylbenzene-1-sulfonyl chloride (pTsCl, 25.9 g, 136 mmol) was added and the reaction mixture was heated at 75° C. for 5 hours. 2-Aminoethanol (166 mL, 2.75 mol) was added after allowing the reaction mixture to cool to room temperature. After one hour, the acetonitrile was evaporated and the crude product was partitioned between ethyl acetate and a saturated aqueous solution of sodium chloride. The layers were separated and the organic layer was evaporated to dryness and then purified on 1.5 kg of silica gel utilizing a gradient of 0-100% ethyl acetate in hexanes to yield tert-butyl 3-(6-amino-3-methylpyridin-2-yl)benzoate (15.2 g, 51%) as a white solid. ESI-MS m/z calc. 284.1, found 285.2 (M+1)+. Retention time 1.16 minutes. 1H NMR (400 MHz, DMSO-d6) δ 7.99-7.98 (m, 1H), 7.90-7.87 (m, 1H) 7.72-7.7.69 (m, 1H), 7.52 (t, J=7.7 Hz, 1H), 7.31 (d, J=8.3 Hz, 1H), 6.42 (d, J=8.3 Hz, 1H), 5.83 (s, 2H), 2.11 (s, 3H), 1.54 (s, 9H).

Workup

  1. temperatureto cool to room temperature
  2. customthe acetonitrile was evaporated
  3. customthe crude product was partitioned between ethyl acetate
  4. customThe layers were separated
  5. customthe organic layer was evaporated to dryness
  6. custompurified on 1.5 kg of silica gel utilizing a gradient of 0-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-e217e18425aa42a19b95bb5e9cd51d9d
Source dataset
uspto-grants-2011_09
Patent number
US08012999B2

Reaction notes

Loading…