Acetic Acid → 2-[4-(1-Methoxy-2-nitro-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl)-piperazin-1-yl]-ethanol

HRID 2276304Notes

Reaction equation

HRID 2276304 reaction equation
[CH3:1][O:2][C:3]1[C:8]2[CH2:9][CH2:10][CH2:11][C:12](=O)[CH2:13][C:7]=2[CH:6]=[CH:5][C:4]=1[N+:15]([O-:17])=[O:16].[N:18]1([CH2:24][CH2:25][OH:26])[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+].[OH-].[Na+]>C(Cl)Cl>[CH3:1][O:2][C:3]1[C:8]2[CH2:9][CH2:10][CH2:11][CH:12]([N:21]3[CH2:22][CH2:23][N:18]([CH2:24][CH2:25][OH:26])[CH2:19][CH2:20]3)[CH2:13][C:7]=2[CH:6]=[CH:5][C:4]=1[N+:15]([O-:17])=[O:16]

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 76771-(2-Hydroxyethyl)piperazineHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 1177782541-Methoxy-2-nitro-5,7,8,9-tetrahydro-6H-benzo[7]annulen-6-one

Product 1

HCID 898152252-[4-(1-Methoxy-2-nitro-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl)-piperazin-1-yl]-ethanolYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

1-Methoxy-2-nitro-5,7,8,9-tetrahydro-benzocyclohepten-6-one (15.09 g, 64.15 mmol) in methylene chloride (870 ml) treated with 2-piperazin-1-yl-ethanol (3 eq) followed by acetic acid (10 eq). The mixture was stirred at 50° C. for 2 hrs and cooled to 0° C. and sodium triacetoxyborohydride (4 eq) was added, then warmed to RT and stirred. After a few hours starting material was still present. Added 0.4 eq further of sodium triacetoxyborohydride, then again after 6 hours. Stirred overnight. Poured into a solution of sat. aq. Sodium bicarbonate and ice and made basic to pH 10 with 1N sodium hydroxide, extracted 2× dichloromethane, dried MgSO4, filtered and concentrated. This material was taken up into ethanol and HCl/ethanol was added. The resulting precipitate was triturated for 2 hours then filtered. The solid was free-based using NaOH followed by sodium bicarbonate and extracted into dichloromethane to give the title compound (19 g, 85% yield). 1H-NMR (400 MHz, CDCl3) 7.56 (d, J=8.2 Hz, 1H), 7.00 (d, J=8.2 Hz, 1H), 3.82 (s, 3H), 3.63-3.06 (m, 2H), 3.29-3.24 (m, 1H), 3.00-2.86 (m, 3H), 2.72-2.67 (m, 2H), 2.60-2.51 (m, 8H), 2.46-2.37 (m, 2H), 2.12-2.07 (m, 2H), 1.87-1.78 (m, 1H), 1.37-1.29 (m, 1H). LC/MS (ESI+) m/z=350 (M+H)+

Workup

  1. temperaturecooled to 0° C.
  2. temperaturewarmed to RT
  3. stirringstirred
  4. waitAfter a few hours starting
  5. waitagain after 6 hours
  6. stirringStirred overnight
  7. extractionextracted 2× dichloromethane, dried MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additionwas added
  11. customThe resulting precipitate was triturated for 2 hours
  12. filtrationthen filtered
  13. extractionextracted into dichloromethane

Sources & evidence

ORD record
ord-ada118e83c7d43a287ee0844d09dbefb
Source dataset
uspto-grants-2015_09
Patent number
US09132128B2

Reaction notes

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