Hydrochloric Acid → Trans-8-chloro-11-nitromethyl-10,11-dihydro-dibenzo[b,f]oxepine-10-carboxylic acid methyl ester

HRID 1970105Notes

Reaction equation

HRID 1970105 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:11]2[CH:12]=[C:13]([Cl:16])[CH:14]=[CH:15][C:10]=2[O:9][C:8]2[CH:17]=[CH:18][CH:19]=[CH:20][C:7]=2[CH:6]=1)=[O:4].C(N=C(N(C)C)N(C)C)(C)(C)C.[N+:33]([CH3:36])([O-:35])=[O:34].Cl>C1COCC1.O.C(OC)(C)(C)C>[CH3:1][O:2][C:3]([C@@H:5]1[C:11]2[CH:12]=[C:13]([Cl:16])[CH:14]=[CH:15][C:10]=2[O:9][C:8]2[CH:17]=[CH:18][CH:19]=[CH:20][C:7]=2[C@H:6]1[CH2:36][N+:33]([O-:35])=[O:34])=[O:4]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6375NitromethaneHCID 35715812-tert-Butyl-1,1,3,3-tetramethylguanidineHCID 58160327Methyl 2-chlorodibenzo[b,f]oxepin-11-carboxylate

Product 1

HCID 59800204Trans-8-chloro-11-nitromethyl-10,11-dihydro-dibenzo[b,f]oxepine-10-carboxylic acid methyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Procedure

To a 5 L 3-neck round bottom flask was added 8-chloro-dibenz[b,f]-oxepin-10-carboxylic acid methyl ester (305 g, 1.06 mol, 1 eq) followed by THF (1.25 L) and t-butyl-tetramethylguanidine (27 g, 0.15 mol, 0.14 eq). To this solution was added nitromethane (576 g, 9.45 mol, 8.9 eq) in THF (0.5 L) while maintaining a temperature of less than 30° C. The resultant mixture was stirred at room temperature until judged complete by HPLC (overnight, <3% starting material). Once complete, methyl tertiary butyl ether (1.25 L), water (0.6 L) and 1N HCl (0.6 L) were added, the layers were separated, and the aqueous layer was extracted a second time with MTBE (1 L). The combined organic layers were washed with 1N HCl (2×0.6 L) and saturated sodium chloride (0.6 L). After addition of toluene (2 L) the organic fraction was concentrated under vacuum to a volume less than 2 L, toluene (1 L) was added, and the mixture was concentrated to minimum volume. Addition of THF (0.5 L) afforded the titled compound as a light colored solution which was used without further purification (368 g, 1.06 mol, theoretical). HPLC area %: 45% toluene, 48% trans-nitro ester, 6% cis-nitro ester, 1% starting material.

Workup

  1. temperaturewhile maintaining a temperature of less than 30° C
  2. customuntil judged complete by HPLC (overnight, <3% starting material)
  3. customthe layers were separated
  4. extractionthe aqueous layer was extracted a second time with MTBE (1 L)
  5. washThe combined organic layers were washed with 1N HCl (2×0.6 L) and saturated sodium chloride (0.6 L)
  6. additionAfter addition of toluene (2 L) the organic fraction
  7. concentrationwas concentrated under vacuum to a volume less than 2 L, toluene (1 L)
  8. additionwas added
  9. concentrationthe mixture was concentrated to minimum volume
  10. additionAddition of THF (0.5 L)

Sources & evidence

ORD record
ord-83ffda31581c4930b39617772ae5438c
Source dataset
uspto-grants-2013_04
Patent number
US08426610B2

Reaction notes

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