Methanesulfonic Acid → HCID 54446811, compound

HRID 1590461Notes

Reaction equation

HRID 1590461 reaction equation
[CH:1](NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:26]=1[N:25]([CH3:27])[C:24]1[CH2:23][CH2:22][CH2:21][C:20](=[O:28])[C:19]2=1.C([N-]C(C)C)(C)C.[Li+].CS(O)(=O)=O.CC1C=CC(COC(NN[C:55]([C:57]2[CH:62]=[N:61][CH:60]=C[N:58]=2)=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.O.C(O)(=O)C>[F:13][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:26]=1[N:25]([CH3:27])[C:24]1[CH2:23][CH2:22][C:21](=[CH:1][C:62]3[N:61]=[CH:60][NH:58][C:57]=3[CH3:55])[C:20](=[O:28])[C:19]2=1

Participants

11

Reactant 7

HCID 6395Methanesulfonic AcidHCID 7912DiisopropylamineHCID 11430Potassium CarbonateHCID 478568p-tolylmethyl N-(pyrazine-2-carbonylamino)carbamateHCID 2724682Lithium diisopropylamideHCID 197698468-Fluoro-9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-oneHCID 178418339Butyllithium

Product 1

HCID 54446811HCID 54446811, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

Diisopropylamine (2.35 ml) in dry THF (15 ml) was cooled to -78° under nitrogen. n-Butyllithium (124 M solution in hexane; 13.4 ml) was added, and the mixture was stirred for 15 min. before cooling to -78°. 8-Fluoro-9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one (3 g) in dry THF (70 ml) was cooled to -78° under nitrogen, the lithium diisopropylamide solution was added, and the resulting mixture was warmed to -40° over 1 h, before re-cooling to -78°. Intermediate 2 (4.9 g) in dry THF (50 ml) was added slowly, and the mixture was allowed to warm to 0° over 3 h. The mixture was re-cooled to -78, acetic acid (20 ml) was added, followed by methanesulphonic acid (50 ml), and the mixture was warmed to 20° and then heated at reflux for 12 h. The cooled mixture was poured into water (400 ml), basified (to pH10) with potassium carbonate (50 g) and extracted with ethyl acetate (3×400 ml). The combined, dried organic extracts were evaporated in vacuo to give an oil which was purified by FCC eluting with System A (100:8:1) to give the title compound (2.79 g), m.p. 260°-264° (decomp.). diisopropylamide solution was added, and the resulting mixture was warmed to -40° over 1 h, before re-cooling to -78°. Intermediate 2 (4.9 l) in dry THF (50 ml) was added slowly, and the mixture was allowed to warm to 0° over 3 h. The mixture was re-cooled to -78°, acetic acid (20 ml) was added, followed by methanesulphonic acid (50 ml), and the mixture was warmed to 20° and then heated at reflux for 12 h. The cooled mixture was poured into water (400 ml), basified (to pH10) with potassium carbonate (50 g) and extracted with ethyl acetate (3×400 ml). The combined, dried organic extracts were evaporated in vacuo to give an oil which was purified by FCC eluting with System A (100:8:1) to give the title compound (2.79 g), m.p. 260°-264° (decomp.).

Workup

  1. temperaturebefore cooling to -78°
  2. temperaturethe resulting mixture was warmed to -40° over 1 h
  3. temperaturebefore re-cooling to -78°
  4. temperatureto warm to 0° over 3 h
  5. additionwas added
  6. temperaturethe mixture was warmed to 20°
  7. temperatureheated
  8. temperatureat reflux for 12 h
  9. extractionextracted with ethyl acetate (3×400 ml)
  10. customdried organic extracts were evaporated in vacuo
  11. customto give an oil which
  12. customwas purified by FCC
  13. washeluting with System A (100:8:1)

Sources & evidence

ORD record
ord-781babe2c3f04fb398103f2d07def8ca
Source dataset
uspto-grants-1993_04
Patent number
US05202343

Reaction notes

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