Triethylamine → HCID 66629381, compound

HRID 1470965Notes

Reaction equation

HRID 1470965 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8](O)[CH2:9][CH2:10][C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][CH:14]=2)O)=[CH:4][CH:3]=1.CCN(CC)CC.CS(Cl)(=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]>C(Cl)Cl.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:9][CH2:10][C@@H:11]([C:13]3[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][CH:14]=3)[N:41]2[C:40]2[CH:42]=[CH:43][C:37]([C:33]([CH3:36])([CH3:35])[CH3:34])=[CH:38][CH:39]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 698614-Tert-ButylanilineHCID 59616825HCID 59616825, compound

Product 1

HCID 66629381HCID 66629381, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of the product from Example 69A (0.60 g, 1.500 mmol) in anhydrous CH2Cl2 (15 mL) at 0° C. was added Et3N (0.627 mL, 4.50 mmol), and the resulting mixture was stirred at 0° C. for 10 min until a homogenous solution was obtained. To the cooled solution was added methanesulfonyl chloride (0.292 mL, 3.75 mmol) dropwise, and the resulting mixture was stirred at 0° C. for 1.5 h until the reaction was complete as determined by TLC (1:1 EtOAc:hexanes). Solvent was removed in vacuo to give a solid, which was dried in vacuo. The solid was dissolved in anhydrous DMF (5 mL), and 4-tert-butylaniline (2.39 mL, 15 mmol) was added. The resulting mixture was stirred at 40° C. for 4 h and then was partitioned between 1N aq. HCl (30 mL) and EtOAc (30 mL). The organic layer was washed with H2O and dried over Na2SO4. The drying agent was filtered off, the solvent was removed in vacuo, and the crude product was purified by column chromatography on silica gel using a solvent gradient of 0-20% EtOAc in hexanes. The title compound was obtained as a colorless solid (0.71 g, 92%). 1H NMR indicated this material was a 87:13 mixture of trans:cis pyrrolidine isomers.

Workup

  1. customwas obtained
  2. stirringthe resulting mixture was stirred at 0° C. for 1.5 h until the reaction
  3. customSolvent was removed in vacuo
  4. customto give a solid, which
  5. customwas dried in vacuo
  6. dissolutionThe solid was dissolved in anhydrous DMF (5 mL)
  7. stirringThe resulting mixture was stirred at 40° C. for 4 h
  8. customwas partitioned between 1N aq. HCl (30 mL) and EtOAc (30 mL)
  9. washThe organic layer was washed with H2O
  10. dry with materialdried over Na2SO4
  11. filtrationThe drying agent was filtered off
  12. customthe solvent was removed in vacuo
  13. customthe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-20% EtOAc in hexanes

Sources & evidence

ORD record
ord-dc1b0f5fb9fa4fc3bb8170ee24f9b222
Source dataset
uspto-grants-2015_04
Patent number
US09006387B2

Reaction notes

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