N-methyl-2-pyrrolidone → 3-nitro-7,8-dihydro-6H-5-oxa-9-aza-benzocycloheptene-9-carboxylic acid 3-dimethylamino-propyl ester

HRID 1687795Notes

Reaction equation

HRID 1687795 reaction equation
[CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][CH2:5][OH:6].CN1CCCC1=O.[H-].[Na+].Cl[CH2:18][CH2:19][CH2:20][N:21]1[C:25]2[CH:26]=[CH:27][C:28]([N+:30]([O-:32])=[O:31])=[CH:29][C:24]=2[O:23][C:22]1=[O:33]>>[CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][CH2:5][O:6][C:22]([N:21]1[C:25]2[CH:26]=[CH:27][C:28]([N+:30]([O-:32])=[O:31])=[CH:29][C:24]=2[O:23][CH2:18][CH2:19][CH2:20]1)=[O:33]

Participants

5

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 24758Sodium hydrideHCID 766463-(Dimethylamino)-1-propanolHCID 672636543-(3-chloro-propyl)-6-nitro-3H-benzoxazol-2-one

Product 1

HCID 672641983-nitro-7,8-dihydro-6H-5-oxa-9-aza-benzocycloheptene-9-carboxylic acid 3-dimethylamino-propyl esterYield 69.3%

Procedure

3-Dimethylamino-propan-1-ol (346 uL, 2.92 mmol) was dissolved in N-methylpyrrolidinone (25.0 mL, 259 mmol) and sodium hydride 60% dispersion in mineral oil (93.5 mg) was added. The reaction was stirred for 5 minutes and then 3-(3-chloro-propyl)-6-nitro-3H-benzoxazol-2-one (500 mg, 1.95 mmol) was added. The reaction was stirred at room temperature for 4 hours and then partitioned between ethyl ether (100 mL) and water (50 mL). The layers were separated and the organic layer was washed twice with water (50 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by basic alumina chromatography using a gradient of 0-50% EtOAc/hex as the eluting solvent to obtain 3-nitro-7,8-dihydro-6H-5-oxa-9-aza-benzocycloheptene-9-carboxylic acid 3-dimethylamino-propyl ester as a yellow oil (437 mg, 69%). LCMS (m/e) 324 (M+H); 1H-NMR (CDCl3, 400 MHz) δ 7.89-7.80 (m, 2H), 7.53-7.36 (m, 1H), 4.29-4.17 (m, 4H), 3.89-3.17 (m, 2H), 2.39-2.08 (m, 4H), 2.19 (s, 6H), 1.88-1.73 (m, 2H).

Workup

  1. stirringThe reaction was stirred at room temperature for 4 hours
  2. custompartitioned between ethyl ether (100 mL) and water (50 mL)
  3. customThe layers were separated
  4. washthe organic layer was washed twice with water (50 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by basic alumina chromatography

Sources & evidence

ORD record
ord-7c5a7fbbdacd4655ac950dc858155f85
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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