Diisopropylamine → 1-tert-Butyl 4-methyl 4-(2-nitro-1-phenylethyl)azepane-1,4-dicarboxylate

HRID 1036705Notes

Reaction equation

HRID 1036705 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[N:13]1([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19][CH2:18][CH2:17][CH:16]([C:20]([O:22][CH3:23])=[O:21])[CH2:15][CH2:14]1.[N+:31](/[CH:34]=[CH:35]/[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)([O-:33])=[O:32]>C1COCC1>[N+:31]([CH2:34][CH:35]([C:16]1([C:20]([O:22][CH3:23])=[O:21])[CH2:17][CH2:18][CH2:19][N:13]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:14][CH2:15]1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)([O-:33])=[O:32]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 5284459beta-nitrostyrene, (E)-HCID 710603801-Tert-butyl 4-methyl azepane-1,4-dicarboxylateHCID 178418339Butyllithium

Product 1

HCID 710601881-tert-Butyl 4-methyl 4-(2-nitro-1-phenylethyl)azepane-1,4-dicarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A cooled (−78° C.) solution of diisopropylamine (667 ul, 4.68 mmol) in THF (dry) (4 ml) was treated with n-BuLi (1.6M in hexanes) (2.93 ml, 4.68 mmol). After 5 minutes, the mixture was allowed to warm to RT and then re-cooled to −78° C. This mixture was added dropwise to a cooled (−78° C.) solution of 1-tert-butyl 4-methyl azepane-1,4-dicarboxylate (step 1) (927 mg, 3.6 mmol) in THF (4 ml). The reaction mixture was stirred at −78° C. for 40 minutes. To this mixture was added (E)-(2-nitrovinyl)benzene (537 mg; 3.6 mmol) in THF (4 ml) and the resulting mixture was allowed to warm slowly to RT. The reaction was quenched with saturated ammonium chloride solution and the mixture was extracted with EtOAc. The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. Purification of the crude product by chromatography on silica eluting with iso-hexane/EtOAc followed by 10-100% TBME in iso-hexane afforded the title compound as a diastereomeric mixture.

Workup

  1. temperaturere-cooled to −78° C
  2. additionThis mixture was added dropwise to
  3. temperatureto warm slowly to RT
  4. customThe reaction was quenched with saturated ammonium chloride solution
  5. extractionthe mixture was extracted with EtOAc
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification of the crude product by chromatography on silica eluting with iso-hexane/EtOAc

Sources & evidence

ORD record
ord-51a39cc882644230b3d7b44fe82aba2b
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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