Ethanolamine → Tert-butyl 3-(2-amino-5-methylpyridin-4-yl)benzoate

HRID 338571Notes

Reaction equation

HRID 338571 reaction equation
[C:1]([O:5][C:6]([C:8]1[CH:9]=[C:10]([C:14]2[CH:19]=[CH:18][N+:17]([O-])=[CH:16][C:15]=2[CH3:21])[CH:11]=[CH:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC1C=CC(S(Cl)(=O)=O)=CC=1.C(C[NH2:36])O>N1C=CC=CC=1.C(#N)C>[NH2:36][C:18]1[CH:19]=[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:15]([CH3:21])=[CH:16][N:17]=1

Participants

6

Reactant 3

HCID 700EthanolamineHCID 73974-Toluenesulfonyl chlorideHCID 578951674-(3-(tert-Butoxycarbonyl)phenyl)-3-methylpyridine 1-oxide

Product 1

HCID 57895160Tert-butyl 3-(2-amino-5-methylpyridin-4-yl)benzoateYield 36.3%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

4-(3-(tert-Butoxycarbonyl)phenyl)-3-methylpyridine 1-oxide (0.467 g, 1.64 mmol) was dissolved in a mixture of pyridine (0.53 mL) and acetonitrile (15 mL) under an atmosphere of argon. 4-Methylbenzene-1-sulfonyl chloride (0.406 g, 2.13 mmol) was added and the reaction mixture was stirred at 75° C. for 72 hours. Ethanolamine (7 mL) was then added and the reaction mixture was allowed to stir for 5 minutes at room temperature. The crude product was partitioned between dichloromethane and a saturated aqueous solution of sodium bicarbonate. The layers were separated and the organic layer was washed with a saturated aqueous solution of sodium chloride. The organic layer was dried over sodium sulfate and then purified on 40 g of silica gel utilizing a gradient of 0-100% ethyl acetate in hexanes to yield the pure product (0.169 g, 0.594 mmol, 36.3%). ESI-MS m/z calc. 284.2. found 285.1 (M+1)+. Retention time of 1.28 minutes. 1H NMR (400.0 MHz, DMSO-d6) δ 7.94-7.91 (m, 1H), 7.84 (s, 1H), 7.79 (d, J=1.7 Hz, 1H), 7.62-7.56 (m, 2H), 6.33 (s, 1H), 5.78 (s, 2H), 1.99 (s, 3H), 1.55 (s, 9H).

Workup

  1. stirringto stir for 5 minutes at room temperature
  2. customThe crude product was partitioned between dichloromethane
  3. customThe layers were separated
  4. washthe organic layer was washed with a saturated aqueous solution of sodium chloride
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. custompurified on 40 g of silica gel utilizing a gradient of 0-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-455825007f8a4b3d925a3427d21dfb67
Source dataset
uspto-grants-2014_11
Patent number
US08889875B2

Reaction notes

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