Pyridine → HCID 68805934, compound

HRID 1796223Notes

Reaction equation

HRID 1796223 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]([F:36])[CH:30]=1>C(OCC)C>[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[F:36])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 1230504-Bromo-2-fluoroanilineHCID 2684721-[(Tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acid

Product 1

HCID 68805934HCID 68805934, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
0 °C

Procedure

Pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (3.8 g, 18 mmol) was dissolved in 150 mL dry diethyl ether under Ar, cooled in an ice water bath, added dry pyridine (8.6 mL, 106 mmol) followed by the dropwise addition of oxalyl chloride (4.6 mL, 53 mmol). A precipitate formed immediately. The reaction was stirred vigorously at 0° C. for one hour, then at ambient temperature for one hour. 100 mL diethyl ether was then added. The solides were filtered off and washed with diethyl ether. The filtrates were concwentrated to an off-white oil. The solid was redissolved oil in 50 mL dry DCM under Ar, cooled to 0° C., and 6 mL pyridine was added, followed by 4-bromo-2-fluoroaniline (3.4 g, 17.7 mmol). The reaction was allowed to warm to ambient temperature, stirred for 3 hours then concentrated. The concentrate was redissolved in 250 mL EtOAc, washed with 10% HCl (3×100 mL), brine (100 mL), dried with MgSO4, filtered and concentrated. The residue was purified on a silica gel column eluted with 20% moving to 40% EtOAc in hexanes to yield title compound as a white solid. (3.2 g, 47%) APCI (AP−): 385.1, 387.1 (M−H)−.

Workup

  1. temperaturecooled in an ice water bath
  2. customA precipitate formed immediately
  3. waitat ambient temperature for one hour
  4. filtrationThe solides were filtered off
  5. washwashed with diethyl ether
  6. dissolutionThe solid was redissolved oil in 50 mL dry DCM under Ar
  7. temperaturecooled to 0° C.
  8. addition6 mL pyridine was added
  9. temperatureto warm to ambient temperature
  10. stirringstirred for 3 hours
  11. concentrationthen concentrated
  12. dissolutionThe concentrate was redissolved in 250 mL EtOAc
  13. washwashed with 10% HCl (3×100 mL), brine (100 mL)
  14. dry with materialdried with MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customThe residue was purified on a silica gel column
  18. washeluted with 20%

Sources & evidence

ORD record
ord-f20bff2d39a74dbd8de3d82d743113b9
Source dataset
uspto-grants-2006_04
Patent number
US07030141B2

Reaction notes

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