Pyridine → HCID 68806399, compound

HRID 2217538Notes

Reaction equation

HRID 2217538 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[CH2:10][C@@H:9]1[C:21]([OH:23])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.C(Cl)(=O)C(Cl)=O.[Br:36][C:37]1[CH:43]=[CH:42][C:40]([NH2:41])=[C:39]([F:44])[CH:38]=1>C(OCC)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[CH2:10][C@@H:9]1[C:21](=[O:23])[NH:41][C:40]1[CH:42]=[CH:43][C:37]([Br:36])=[CH:38][C:39]=1[F:44])=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 1230504-Bromo-2-fluoroanilineHCID 68806846HCID 68806846, compound

Product 1

HCID 68806399HCID 68806399, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(2R,4R)-4-(tert-Butyl-dimethyl-silanyloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (1.54 g, 4.5 mmol) was dissolved in 50 mL diethyl ether under an Ar atmosphere, cooled in an ice water bath, added dry pyridine (1.4 mL, 17.8 mmol), followed by the dropwise addition of oxalyl chloride (0.58 mL, 6.7 mmol). Reaction was stirred at 0° C. for 1 hour, then at ambient temperature for 1 hour. Diluted reaction with 50 mL diethyl ether, filtered off solids and concentrated filtrates. Redissolved filtrate in 30-mL dry DCM under an Ar atmosphere, cooled in an ice water bath, added 1 mL dry pyridine followed by 4-bromo-2-fluoroaniline (0.85 g, 4.5 mmol). Stirred reaction at ambient temperature for 20 hours. Concentrated solution, redissolved in EtOAc (150 mL), washed with 10% citric acid (3×100 mL), water (2×100 mL), brine, dried with MgSO4, filtered and concentrated. Purified on a silica gel column eluting with an automated system with gradient of 0-60% EtOAc in hexanes over 40 minutes. Combined and concentrated pure fractions to yield title compound as a clear oil. (0.96 g, 42%) APCI (AP−): 515.1, 517.1 (M−H)−.

Workup

  1. temperaturecooled in an ice water bath
  2. customReaction
  3. waitat ambient temperature for 1 hour
  4. additionDiluted
  5. filtrationfiltered off solids and concentrated filtrates
  6. temperatureRedissolved filtrate in 30-mL dry DCM under an Ar atmosphere, cooled in an ice water bath
  7. additionadded 1 mL dry pyridine
  8. stirringStirred
  9. customreaction at ambient temperature for 20 hours
  10. washwashed with 10% citric acid (3×100 mL), water (2×100 mL), brine
  11. dry with materialdried with MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customPurified on a silica gel column
  15. washeluting with an automated system with gradient of 0-60% EtOAc in hexanes over 40 minutes
  16. concentrationconcentrated pure fractions

Sources & evidence

ORD record
ord-ff45068b12f146a6ba09378d7f989161
Source dataset
uspto-grants-2008_08
Patent number
US07407974B2

Reaction notes

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