Triethylamine → Isopropyl 4-fluoro-3-[(6-methyl-2,3-dihydro-1,4-oxathiine-5-carbonyl)amino]benzoate

HRID 1938848Notes

Reaction equation

HRID 1938848 reaction equation
S(Cl)(Cl)=O.[CH3:5][C:6]1[O:7][CH2:8][CH2:9][S:10][C:11]=1[C:12]([OH:14])=O.[NH2:15][C:16]1[CH:17]=[C:18]([CH:25]=[CH:26][C:27]=1[F:28])[C:19]([O:21][CH:22]([CH3:24])[CH3:23])=[O:20].C(N(CC)CC)C>C(Cl)Cl>[CH3:5][C:6]1[O:7][CH2:8][CH2:9][S:10][C:11]=1[C:12]([NH:15][C:16]1[CH:17]=[C:18]([CH:25]=[CH:26][C:27]=1[F:28])[C:19]([O:21][CH:22]([CH3:24])[CH3:23])=[O:20])=[O:14]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 5399462-Methyl-5,6-dihydro-1,4-oxathiine-3-carboxylic acidHCID 214702561-Methylethyl 3-amino-4-fluorobenzoate

Product 1

HCID 507309Isopropyl 4-fluoro-3-[(6-methyl-2,3-dihydro-1,4-oxathiine-5-carbonyl)amino]benzoateYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Thionyl chloride (4.6 g, 0.039 mole) was added to a stirred mixture of 5,6-dihydro-2-methyl-1,4-oxathiin-3-carboxylic acid (6.0 g, 0.037 mole) and methylene chloride (50 ml). The mixture was warmed to 35°-40° C. for about 3 hours, then evaporated under reduced pressure. The residue, crude 5,6-dihydro-2-methyl-1,4-oxathiin-3-carbonyl chloride, was dissolved in methylene chloride (50 ml) and the ice-cooled solution treated dropwise with a solution of 1-methylethyl 3-amino-4-fluorobenzoate (7.4 g, 0.037 mole) and triethylamine (3.9 g, 0.039 mole) in methylene chloride (50 ml). The reaction mixture was stirred overnight at room temperature, and then washed in sequence with water (50 ml), dilute hydrochloric acid (3.5%, 50 ml), water (50 ml), dilute sodium hydroxide (2%, 25 ml) and water (50 ml), dried with anhydrous sodium sulfate and evaporated. Recrystallization of the solid residue from 100% ethanol (100 ml) gave light brown crystals, m.p. 132°-135° C. (7.8 g, 61% yield).

Workup

  1. temperatureThe mixture was warmed to 35°-40° C. for about 3 hours
  2. customevaporated under reduced pressure
  3. dissolutionThe residue, crude 5,6-dihydro-2-methyl-1,4-oxathiin-3-carbonyl chloride, was dissolved in methylene chloride (50 ml)
  4. temperaturethe ice-cooled solution
  5. washwashed in sequence with water (50 ml), dilute hydrochloric acid (3.5%, 50 ml), water (50 ml), dilute sodium hydroxide (2%, 25 ml) and water (50 ml)
  6. dry with materialdried with anhydrous sodium sulfate
  7. customevaporated
  8. customRecrystallization of the solid residue from 100% ethanol (100 ml)
  9. customgave light brown crystals, m.p. 132°-135° C. (7.8 g, 61% yield)

Sources & evidence

ORD record
ord-dc3f294f4b7d49ca97a6055435021b13
Source dataset
uspto-grants-1997_12
Patent number
US05693827

Reaction notes

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