4-Tert-Butylaniline → HCID 86649103, compound

HRID 2360096Notes

Reaction equation

HRID 2360096 reaction equation
CS(O[C@@H:6]([C:24]1[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=1)[CH2:7][CH2:8][C@@H:9](OS(C)(=O)=O)[C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=1)(=O)=O.[C:33]([C:37]1[CH:43]=[CH:42][C:40]([NH2:41])=[CH:39][CH:38]=1)([CH3:36])([CH3:35])[CH3:34]>CC1CCCO1.Cl>[C:33]([C:37]1[CH:38]=[CH:39][C:40]([N:41]2[C@H:9]([C:10]3[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=3)[CH2:8][CH2:7][C@H:6]2[C:24]2[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=2)=[CH:42][CH:43]=1)([CH3:36])([CH3:34])[CH3:35]

Participants

5

Reactant 2

HCID 698614-Tert-ButylanilineHCID 58032014HCID 58032014, compound

Product 1

HCID 86649103HCID 86649103, compoundYield 51.6%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To the crude product solution (1R,4R)-1,4-bis(4-nitrophenyl)butane-1,4-diyl dimethanesulfonate (7.35 g, 13.39 mmol) was added 4-tert-butylaniline (13.4 g, 90 mmol) at 23° C. over 1 minute. The reaction was heated to 65° C. for 2 h. After completion, the reaction mixture was cooled to 23° C. and diluted with 2-methyltetrahydrofuran (100 mL) and 1 M HCl (150 mL). After partitioning the phases, the organic phase was treated with 1 M HCl (140 mL), 2-methyltetrahydrofuran (50 mL), and 25 wt % aq. NaCl (100 mL), and the phases were partitioned. The organic phase was washed with 25 wt % aq. NaCl (50 mL), dried over MgSO4, filtered, and concentrated in vacuo to approximately 20 mL. Heptane (30 mL) and additional 2-methyltetrahydrofuran were added in order to induce crystallization. The slurry was concentrated further, and additional heptane (40 mL) was slowly added and the slurry was filtered, washing with 2-methyltetrahydrofuran:heptane (1:4, 20 mL). The solids were suspended in MeOH (46 mL) for 3 h, filtered, and the wet solid was washed with additional MeOH (18 mL). The solid was dried at 45° C. in a vacuum oven for 16 h to provide (2S,5S)-1-(4-tert-butylphenyl)-2,5-bis(4-nitrophenyl)pyrrolidine (3.08 g, 51% 2-step yield).

Workup

  1. temperatureAfter completion, the reaction mixture was cooled to 23° C.
  2. customAfter partitioning the phases
  3. additionthe organic phase was treated with 1 M HCl (140 mL), 2-methyltetrahydrofuran (50 mL), and 25 wt % aq. NaCl (100 mL)
  4. customthe phases were partitioned
  5. washThe organic phase was washed with 25 wt % aq. NaCl (50 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo to approximately 20 mL
  9. additionHeptane (30 mL) and additional 2-methyltetrahydrofuran were added in order
  10. customcrystallization
  11. concentrationThe slurry was concentrated further
  12. additionadditional heptane (40 mL) was slowly added
  13. filtrationthe slurry was filtered
  14. washwashing with 2-methyltetrahydrofuran:heptane (1:4, 20 mL)
  15. filtrationfiltered
  16. washthe wet solid was washed with additional MeOH (18 mL)
  17. customThe solid was dried at 45° C. in a vacuum oven for 16 h

Sources & evidence

ORD record
ord-c8487ca8a84a41dd95ed47cdbcc2d420
Source dataset
uspto-grants-2014_04
Patent number
US08686026B2

Reaction notes

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