N-methyl-2-pyrrolidone → (S)-8-Nitro-2,3,3a,4-tetrahydro-1H-5-oxa-10b-aza-benzo[e]azulen-6-one

HRID 1686896Notes

Reaction equation

HRID 1686896 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[C:5]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[CH:7][C:6]=1F)[CH3:2].C(N(C(C)C)CC)(C)C.C[N:26]1C(=O)[CH2:29][CH2:28][CH2:27]1>>[N+:11]([C:9]1[CH:8]=[CH:7][C:6]2[N:26]3[C@H:2]([CH2:1][O:3][C:4](=[O:15])[C:5]=2[CH:10]=1)[CH2:29][CH2:28][CH2:27]3)([O-:13])=[O:12]

Participants

4

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 12793176Ethyl 2-fluoro-5-nitrobenzoate

Product 1

HCID 67264709(S)-8-Nitro-2,3,3a,4-tetrahydro-1H-5-oxa-10b-aza-benzo[e]azulen-6-one

Conditions

Temperature
100 °C

Procedure

By adopting a similar procedure as described in “Mueller, W; Stauss, U.; Forschungsinst, W.; Bern, S. Helvetica Chimica Acta 1982, 65, 2118.” (S)-8-Nitro-2,3,3a,4-tetrahydro-1H-5-oxa-10b-aza-benzo[e]azulen-6-one was prepared as follows. A mixture of 2-fluoro-5-nitro-benzoic acid ethyl ester (1.16 g, 5.44 mmol.), S-prolinol (638 mg, 6.31 mmol) and diisopropylethylamine (1.5 mL, 8.62 mmol) in dry NMP (20 mL) was stirred at 100° C. for 3 h. Solvent was removed and the mixture was partition between EtOAc and water. Organic layer was extracted two more times with EtOAc. Combined organic was washed successively with water (twice) and brine. After drying over magnesium sulfate, solvent was evaporated. The product, (S)-8-Nitro-2,3,3a,4-tetrahydro-1H-5-oxa-10b-aza-benzo[e]azulen-6-one was obtained as a solid (1.08 g, 80%).

Workup

  1. custom” (S)-8-Nitro-2,3,3a,4-tetrahydro-1H-5-oxa-10b-aza-benzo[e]azulen-6-one was prepared
  2. customSolvent was removed
  3. customthe mixture was partition between EtOAc and water
  4. extractionOrganic layer was extracted two more times with EtOAc
  5. washCombined organic was washed successively with water (twice) and brine
  6. dry with materialAfter drying over magnesium sulfate, solvent
  7. customwas evaporated

Sources & evidence

ORD record
ord-a6a738649997400c8b858de1635012c5
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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