Potassium Carbonate → 6-[4-(2-Tert-butoxycarbonylamino-2-carboxy-ethyl)-phenoxy]-nicotinic acid methyl ester

HRID 273437

Reaction equation

HRID 273437 reaction equation
C(=O)([O-])[O-].[K+].[K+].Cl[C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][N:9]=1.[C:18]([NH:25][C@H:26]([C:35]([OH:37])=[O:36])[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([OH:34])=[CH:30][CH:29]=1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>CN(C=O)C.O>[CH3:15][O:14][C:12](=[O:13])[C:11]1[CH:16]=[CH:17][C:8]([O:34][C:31]2[CH:30]=[CH:29][C:28]([CH2:27][CH:26]([NH:25][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:35]([OH:37])=[O:36])=[CH:33][CH:32]=2)=[N:9][CH:10]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 117439L-Tyrosine, N-(1,1-dimethylethoxy)carbonyl-HCID 254249Methyl 6-chloropyridine-3-carboxylate

Product 1

HCID 692036526-[4-(2-Tert-butoxycarbonylamino-2-carboxy-ethyl)-phenoxy]-nicotinic acid methyl esterYield 94.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Potassium carbonate (1.23 g, 8.9 mmol) and methyl 6-chloronicotinate (1.8 g, 10.66 mmol) were added to a solution of Boc-tyrosine (1.0 g, 3.55 mmol) in anhydrous DMF (15 mL). The resulting suspension was refluxed at 70 deg C. under an atmosphere of argon. After 72 hrs, the reaction mixture was cooled to room temperature, diluted with water (100 mL) and extracted with EtOAc (2×100 mL). The aqueous layer was collected, acidified with 5.0 M HCl to pH ˜2.5 and extracted with EtOAc (2×100 mL). The resulting EtOAc layer was extracted with water (1×150 mL) and brine (1×150 mL), dried over anhydrous magnesium sulfate, filtered and concentrated and flash chromatographed (30-40% ethyl acetate in hexane with 1% acetic acid) to yield desired ester, 17 as a solid (1.4 g). 1H NMR (400 MHz, DMSO-d6): 12.45 (s, 1H), 8.68 (br, 1H), 8.29 (dd, J=8.4 and 2.4 Hz, 1H), 7.31 (d, J=8.4 Hz, 2H), 7.14 (d, J=8.8 Hz, 1H), 7.08 (m, 3H), 4.12 (m, 1H), 3.85 (s, 3H), 3.05 (dd, J=14.0 and 4.0 Hz, 1H), 2.84 (dd, J=14.0 and 10.8 Hz, 1H) 1.33 (s, 9H)

Workup

  1. temperatureThe resulting suspension was refluxed at 70 deg C
  2. extractionextracted with EtOAc (2×100 mL)
  3. customThe aqueous layer was collected
  4. extractionextracted with EtOAc (2×100 mL)
  5. extractionThe resulting EtOAc layer was extracted with water (1×150 mL) and brine (1×150 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customflash chromatographed (30-40% ethyl acetate in hexane with 1% acetic acid)

Sources & evidence

ORD record
ord-5a23609a9bab4bc1867c5c970fb2d706
Source dataset
uspto-grants-2008_11
Patent number
US07456292B2

Linked notes

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