Oxalyl chloride → HCID 90412491, compound

HRID 1526662Notes

Reaction equation

HRID 1526662 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([F:12])[C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[NH2:19][C:20]1[CH:21]=[CH:22][C:23]([F:37])=[C:24]([C@:26]2([CH:34]([F:36])[F:35])[C@@H:32]3[C@@H:30]([CH2:31]3)[O:29][C:28]([NH2:33])=[N:27]2)[CH:25]=1.C(N(C(C)C)CC)(C)C>ClCCl.CN(C=O)C>[NH2:33][C:28]1[O:29][C@H:30]2[C@@H:32]([C@:26]([C:24]3[CH:25]=[C:20]([NH:19][C:4](=[O:6])[C:3]4[C:7]([F:12])=[CH:8][C:9]([F:11])=[CH:10][C:2]=4[F:1])[CH:21]=[CH:22][C:23]=3[F:37])([CH:34]([F:35])[F:36])[N:27]=1)[CH2:31]2

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 5203732,4,6-Trifluorobenzoic acidHCID 90401262HCID 90401262, compound

Product 1

HCID 90412491HCID 90412491, compoundYield 69.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2,4,6-trifluorobenzoic acid (120 mg, 0.681 mmol, Aldrich) in dichloromethane (2 mL) was added oxalyl chloride (0.242 mL, 2.73 mmol, Aldrich), followed by catalytic amounts of DMF (20 μL). The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in DCM (2 mL). This solution was added dropwise to a separate solution of (1R,5S,6R)-5-(5-amino-2-fluorophenyl)-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine (185 mg, 0.682 mmol) and diisopropylethylamine (0.12 mL, 0.682 mmol) in dichloromethane (2.5 mL) cooled to 0° C. After completed addition, the reaction mixture was stirred for 20 min at 0° C. The reaction mixture was quenched with aqueous saturated sodium bicarbonate solution and extracted with DCM (2×3 mL). The combined organic extracts were dried over MgSO4 and concentrated under reduced pressure. The residue was dissolved in MeOH (1.5 mL) and cooled to 0° C. H2O (4 mL) was added to the solution and the mixture was stirred at 0° C. for 1 h. The white solid was filtered off, washed with H2O and dried in under reduced pressure to give 203 mg of the title compound as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in DCM (2 mL)
  3. temperaturecooled to 0° C
  4. additionaddition
  5. stirringthe reaction mixture was stirred for 20 min at 0° C
  6. customThe reaction mixture was quenched with aqueous saturated sodium bicarbonate solution
  7. extractionextracted with DCM (2×3 mL)
  8. dry with materialThe combined organic extracts were dried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. dissolutionThe residue was dissolved in MeOH (1.5 mL)
  11. temperaturecooled to 0° C
  12. additionH2O (4 mL) was added to the solution
  13. stirringthe mixture was stirred at 0° C. for 1 h
  14. filtrationThe white solid was filtered off
  15. washwashed with H2O
  16. customdried in under reduced pressure

Sources & evidence

ORD record
ord-c3fd70a15f284c9c9f9b2ff223cceb9c
Source dataset
uspto-grants-2015_07
Patent number
US09085576B2

Reaction notes

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