1,2-Dichloroethane → 4-(1-methoxy-2-nitro-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-yl)-morpholine

HRID 1041164Notes

Reaction equation

HRID 1041164 reaction equation
[CH3:1][O:2][C:3]1[C:8]2[CH2:9][CH2:10][C:11](=O)[CH2:12][CH2:13][C:7]=2[CH:6]=[CH:5][C:4]=1[N+:15]([O-:17])=[O:16].ClCCCl.[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>>[CH3:1][O:2][C:3]1[C:8]2[CH2:9][CH2:10][CH:11]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[CH2:12][CH2:13][C:7]=2[CH:6]=[CH:5][C:4]=1[N+:15]([O-:17])=[O:16]

Participants

7

Reactant 6

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 8083MorpholineHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 672641411-Methoxy-2-nitro-8,9-dihydro-5H-benzo[7]annulen-7(6H)-one

Product 1

HCID 672641014-(1-methoxy-2-nitro-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-yl)-morpholineYield 78.3%

Procedure

To a stirred solution of 1-methoxy-2-nitro-5,6,8,9-tetrahydro-benzocyclohepten-7-one (236 mg, 0.00100 mol) in 1,2-dichloroethane (8 mL, 0.1 mol) at room temperature was added morpholine (0.23 mL, 0.0026 mol) followed by acetic acid (0.15 mL, 0.0026 mol) dropwise. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was cooled to 0° C. and sodium triacetoxyborohydride was added in one portion. The reaction mixture was stirred at 0° C. for 2 h then warmed to room temperature overnight. Workup involved addition of 1N NaOH to bring pH to ˜10. The reaction mixture was extracted with ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered and concentrated in vacuo to a orange oil. Purification was accomplished using ISCO chromatography on silica gel using hexane-ethyl acetate and methylene chloride-methanol to give 4-(1-methoxy-2-nitro-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-yl)-morpholine as a yellow solid (0.24 g, 78%). 1H NMR (400 MHz, CDl3) δ 6.70 (s, 1H, J=7.92 Hz), 6.51 (d, 1H, J=7.88), 3.70 (m, 9H), 3.29 (q, 1H, J=14.41, 8 Hz), 2.74 (q, 1H, J=14.28, 7.48 Hz), 2.55 (m, 6H), 2.31 (m, 1H), 2.10 (m, 2H), 1.35 (m, 2H).

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. stirringThe reaction mixture was stirred at 0° C. for 2 h
  3. temperaturethen warmed to room temperature overnight
  4. extractionThe reaction mixture was extracted with ethyl acetate
  5. washwashed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo to a orange oil
  9. customPurification

Sources & evidence

ORD record
ord-cadceac52d0540d38753aa39efe32204
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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