Water → 3-Bromomethyl-7-(2,6-difluorobenzyl)-4,7-dihydro-5-isobutyryl-2-(4-nitrophenyl)-4-oxothieno[2,3-b]pyridine

HRID 2304880Notes

Reaction equation

HRID 2304880 reaction equation
[Br:1][CH2:2][C:3]1[C:11]2[C:10](=[O:12])[C:9]([C:13](=[O:17])[CH:14]([CH3:16])[CH3:15])=[CH:8][N:7]([CH2:18][C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])[C:6]=2[S:5][C:4]=1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[N+:33]([O-])([O-:35])=[O:34].[Na+].O>CS(O)(=O)=O.C(OCC)(=O)C>[Br:1][CH2:2][C:3]1[C:11]2[C:10](=[O:12])[C:9]([C:13](=[O:17])[CH:14]([CH3:16])[CH3:15])=[CH:8][N:7]([CH2:18][C:19]3[C:20]([F:26])=[CH:21][CH:22]=[CH:23][C:24]=3[F:25])[C:6]=2[S:5][C:4]=1[C:27]1[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=1

Participants

6

Reactant 3

HCID 962WaterHCID 24268Sodium NitrateHCID 184586143-Bromomethyl-7-(2,6-difluorobenzyl)-4,7-dihydro-5-isobutyryl-4-oxo-2-phenylthieno[2,3-b]pyridine

Product 1

HCID 155504633-Bromomethyl-7-(2,6-difluorobenzyl)-4,7-dihydro-5-isobutyryl-2-(4-nitrophenyl)-4-oxothieno[2,3-b]pyridineYield 74.5%

Reagents, catalysts & solvents 2

HCID 6395Methanesulfonic AcidSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
14 °C

Procedure

3-Bromomethyl-7-(2,6-difluorobenzyl)-4,7-dihydro-5-isobutyryl-4-oxo-2-phenylthieno[2,3-b]pyridine (40 g) was dissolved in methanesulfonic acid (200 ml) with cooling at 13 to 15° C. and then treated dropwise with a solution of sodium nitrate (6.59 g) in methanesulfonic acid (100 ml) over a period of 1 hour. The mixture was stirred as it was for 2.5 hours, and then poured into a cool water (2800 ml), and the crystal precipitated was recovered by a filtration, washed with water until the pH of the wash became 5 to 6, and then dried in vacuo at 50° C. for 24 hours. The rude crystal thus obtained was suspended in ethyl acetate (300 ml), and the reaction mixture was stirred at 50° C. for 1 hour and then with cooling on ice for 1 hour, and the crystal was recovered by a filtration, washed with a cooled ethyl acetate (100 ml), dried in vacuo at 40° C. for 5 hours to obtain the title compound (32.4 g, 74.5%).

Workup

  1. customthe crystal precipitated
  2. filtrationwas recovered by a filtration
  3. washwashed with water until the pH of the wash
  4. customdried in vacuo at 50° C. for 24 hours
  5. customThe rude crystal thus obtained
  6. stirringthe reaction mixture was stirred at 50° C. for 1 hour
  7. temperaturewith cooling on ice for 1 hour
  8. filtrationthe crystal was recovered by a filtration
  9. washwashed with a cooled ethyl acetate (100 ml)
  10. customdried in vacuo at 40° C. for 5 hours

Sources & evidence

ORD record
ord-d07176f291cd4952b30302aa91210c48
Source dataset
uspto-grants-2002_08
Patent number
US06437132B2

Reaction notes

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