Acetic Acid → HCID 67263579, compound

HRID 1041234Notes

Reaction equation

HRID 1041234 reaction equation
COC1C([N+]([O-])=O)=CC2CCC(=O)CCC=2C=1.[CH3:18][O:19][C:20]1[C:21]([N+:37]([O-:39])=[O:38])=[CH:22][C:23]2[CH2:29][CH2:28][CH:27]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[CH2:26][CH2:25][C:24]=2[CH:36]=1.C(Cl)Cl.N1CCOCC1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH3:18][O:19][C:20]1[C:21]([N+:37]([O-:39])=[O:38])=[CH:22][C:23]2[CH2:29][CH2:28][CH:27]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[CH2:26][CH2:25][C:24]=2[CH:36]=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 86633970HCID 86633970, compound

Product 1

HCID 67263579HCID 67263579, compoundYield 84.1%

Procedure

4-(2-Methoxy-3-nitro-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-yl)-morpholine 2-Methoxy-3-nitro-5,6,8,9-tetrahydro-benzocyclohepten-7-one (4.94 g, 0.0210 mol) in Methylene chloride (100 mL, 2 mol) was treated with Morpholine (18.30 g, 0.2100 mol) and then Acetic acid (12.61 g, 0.2100 mol). Two mass equivalents of powdered 4A molecular sieves were added and the mixture was heated to reflux and was allowed to stir for 4 hours. The solution was then cooled to room temp and Sodium triacetoxyborohydride (8.90 g, 0.0420 mol) was added. The reaction was then allowed to proceed until HPLC showed consumption of starting material. The reaction mixture was poured over saturated sodium bicarbonate, and organics were extracted with ethyl acetate/dichloromethane. Combined organics were dried over sodium sulfate, filtered and reduced en vacuo. The crude mixture was purified by Isco flash column chromatography (DCM/MeOH). Combined fractions were reduced en vacuo to afford 5.41 grams (84%) of 4-(2-Methoxy-3-nitro-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-yl)-morpholine. 4-(2-Methoxy-1-nitro-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-yl)-morpholine was made in an analogous manner using the same conditions described above.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux
  3. customconsumption of starting material
  4. additionThe reaction mixture was poured over saturated sodium bicarbonate
  5. extractionorganics were extracted with ethyl acetate/dichloromethane
  6. dry with materialCombined organics were dried over sodium sulfate
  7. filtrationfiltered
  8. customThe crude mixture was purified by Isco flash column chromatography (DCM/MeOH)

Sources & evidence

ORD record
ord-4938d9c18ea14868a896a700bfa1adc9
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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