Pyridine → HCID 68807453, compound

HRID 1796232Notes

Reaction equation

HRID 1796232 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.[Cl:28][C:29]1[CH:35]=[C:34]([Br:36])[CH:33]=[CH:32][C:30]=1[NH2:31]>C(OCC)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13](=[O:15])[NH:31][C:30]1[CH:32]=[CH:33][C:34]([Br:36])=[CH:35][C:29]=1[Cl:28])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 2684721-[(Tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acidHCID 6101694-Bromo-2-chloroaniline

Product 1

HCID 68807453HCID 68807453, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (2.2 g, 10 mmol) was dissolved in 150 mL dry diethyl ether under Ar, cooled in an ice water bath, added dry pyridine (2.8 mL, 34 mmol) followed by the dropwise addition of oxalyl chloride (1.5 mL, 17 mmol). A precipitate forms immediately. The reaction was stirred vigorously at 0° C. for 1 hours, then at ambient temperature for two hours. Added 100 mL diethyl ether, filtered off solids washing with diethyl ether. Concentrated the filtrates to an off-white oil. Redissolved oil in 100 mL dry DCM under Ar, cooled to 0° C., added 3 mL pyridine followed by 2-chloro-4-bromoaniline (1.8 g, 8.5 mmol). The reaction was allowed to warm to ambient temperature and stirred over the weekend. Concentrated reaction, redissolved in 250 mL EtOAc, washed with 10% citric acid (3×100 mL), water, (2×100 mL), brine (100 mL), dried with MgSO4, filtered and concentrated. Purified on a silica gel column eluted with an automated system with gradient of 0-60% EtOAc in hexanes. Combined and concentrated pure fractions to yield title compound as a yellow solid. (2.7 g, 79%) APCI (AP−): 401.0, 403.0, 405.0 (M−H)−.

Workup

  1. temperaturecooled in an ice water bath
  2. waitat ambient temperature for two hours
  3. filtrationfiltered off solids
  4. washwashing with diethyl ether
  5. concentrationConcentrated the filtrates to an off-white oil
  6. dissolutionRedissolved oil in 100 mL dry DCM under Ar
  7. temperaturecooled to 0° C.
  8. additionadded 3 mL pyridine
  9. temperatureto warm to ambient temperature
  10. stirringstirred over the weekend
  11. concentrationConcentrated
  12. customreaction
  13. washwashed with 10% citric acid (3×100 mL), water, (2×100 mL), brine (100 mL)
  14. dry with materialdried with MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customPurified on a silica gel column
  18. washeluted with an automated system with gradient of 0-60% EtOAc in hexanes
  19. concentrationconcentrated pure fractions

Sources & evidence

ORD record
ord-3f2d0813c00744328dfbb27b394008a2
Source dataset
uspto-grants-2006_04
Patent number
US07030141B2

Reaction notes

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