Ethyl bromodifluoroacetate → HCID 71143765, compound

HRID 1396213Notes

Reaction equation

HRID 1396213 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([F:26])([F:25])[C:9]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=2[F:24])([OH:16])[CH2:10][N:11]2[CH:15]=[N:14][N:13]=[N:12]2)=[N:6][CH:7]=1.BrC(F)([F:34])C(OCC)=O.BrC1C=CC(F)=CN=1>CS(C)=O.[Cu]>[F:24][C:18]1[CH:19]=[C:20]([F:23])[CH:21]=[CH:22][C:17]=1[C:9]([OH:16])([CH2:10][N:11]1[CH:15]=[N:14][N:13]=[N:12]1)[C:8]([F:26])([F:25])[C:5]1[CH:4]=[CH:3][C:2]([F:34])=[CH:7][N:6]=1

Participants

6

Reactant 3

HCID 69585Ethyl bromodifluoroacetateHCID 27831712-Bromo-5-fluoropyridineHCID 71142816HCID 71142816, compound

Product 1

HCID 71143765HCID 71143765, compound

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

Compound 10 was prepared in a similar manner to compound 1. To a stirred solution of ethyl 2-bromo-2,2-difluoroacetate (2.18 mL, 17.0 mmol) in DMSO (18 mL) was added copper powder (2.16 g, 34.0 mmol) at RT under N2 atmosphere. After being stirred for 2 h at RT, 2-bromo-5-fluoropyridine (1.50 g, 8.52 mmol) was then added, and stirring was continued for 3 h at RT. The progress of the reaction was monitored by TLC. The reaction was quenched with aqueous NH4Cl and extracted with CH2Cl2 (3×50 mL). The combined organic layers were washed with water and brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford crude product mixture. Purification by column chromatography (eluting with EtOAc/hexane) afforded the ester (1.40 g, 6.3 mmol, 77%) as a pale yellow oil. 1H NMR (500 MHz, CDCl3): δ 8.50 (s, 1H), 7.78 (dd, J=9.0, 4.0 Hz, 1H), 7.60-7.51 (m, 1H), 4.42-4.32 (m, 2H), 1.39-1.31 (m, 3H). MS (ESI): m/z 220 [M++1].

Workup

  1. stirringstirring
  2. waitwas continued for 3 h at RT
  3. customThe reaction was quenched with aqueous NH4Cl
  4. extractionextracted with CH2Cl2 (3×50 mL)
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customto afford crude product mixture
  9. customPurification
  10. washby column chromatography (eluting with EtOAc/hexane)

Sources & evidence

ORD record
ord-7703e03260e34c219132ccd0bcc505d1
Source dataset
uspto-grants-2014_12
Patent number
US08901121B2

Reaction notes

Loading…