Pyridine → HCID 68808253, compound

HRID 2217423Notes

Reaction equation

HRID 2217423 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.C(Cl)(=O)C(Cl)=O.[Br:28][C:29]1[CH:35]=[CH:34][C:32]([NH2:33])=[C:31]([CH3:36])[CH:30]=1>C(OCC)C.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13](=[O:15])[NH:33][C:32]1[CH:34]=[CH:35][C:29]([Br:28])=[CH:30][C:31]=1[CH3:36])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 1049Pyridine2×HCID 114234-Bromo-2-methylanilineHCID 65578Oxalyl chlorideHCID 2684721-[(Tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acid

Product 1

HCID 68808253HCID 68808253, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (2 g, 9.3 mmol) was dissolved in 100 mL dry diethyl ether under Ar, cooled in an ice water bath, added dry pyridine (4.5 mL, 55 mmol) followed by the dropwise addition of oxalyl chloride (2.4 mL, 27 mmol). A precipitate forms immediately. The reaction was stirred vigorously at 0° C. for one hour, then at ambient temperature for one hour. Added 100 mL diethyl ether, filtered off solids washing with diethyl ether. Concentrated the filtrates to an off white oil. Redissolved (0.95 g, 4.0 mmol) oil in 40 mL dry DCM under Ar, cooled to 0° C., added 1.3 mL pyridine followed by 4-bromo-2-methylaniline (0.75 g, 4.0 mmol). The reaction was allowed to warm to ambient temperature, stirred overnight then concentrated. Redissolved in 100 mL EtOAc, washed with 1 N HCl (3×50 mL), brine (100 mL), dried with MgSO4, filtered and concentrated to yield title compound. (1.09 g, 70%) APCI (AP−): 381.0, 383.0 (M−H)−.

Workup

  1. temperaturecooled in an ice water bath
  2. waitat ambient temperature for one hour
  3. filtrationfiltered off solids
  4. washwashing with diethyl ether
  5. concentrationConcentrated the filtrates to an off white oil
  6. temperaturecooled to 0° C.
  7. temperatureto warm to ambient temperature
  8. stirringstirred overnight
  9. concentrationthen concentrated
  10. dissolutionRedissolved in 100 mL EtOAc
  11. washwashed with 1 N HCl (3×50 mL), brine (100 mL)
  12. dry with materialdried with MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-74d29827a5be485cb673a39753f6687b
Source dataset
uspto-grants-2008_08
Patent number
US07407972B2

Reaction notes

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