Water → HCID 59452684, compound

HRID 419440Notes

Reaction equation

HRID 419440 reaction equation
C(Cl)(=O)C(Cl)=O.[N+:7]([C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH2:21][CH2:20][CH:19]([OH:22])[CH2:18][CH2:17]2)=[CH:12][C:11]=1[O:23][CH2:24][C:25]([F:28])([F:27])[F:26])([O-:9])=[O:8].O>C(Cl)Cl.CS(C)=O>[N+:7]([C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH2:21][CH2:20][C:19](=[O:22])[CH2:18][CH2:17]2)=[CH:12][C:11]=1[O:23][CH2:24][C:25]([F:28])([F:26])[F:27])([O-:9])=[O:8]

Participants

6

Reactant 3

HCID 962WaterHCID 65578Oxalyl chlorideHCID 59452678HCID 59452678, compound

Product 1

HCID 59452684HCID 59452684, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (4.3 mL, 2.0M in DCM, 8.6 mmol) in 40 mL of DCM was cooled to −78° C. with stirring. DMSO (1.2 mL, 17 mmol) was added dropwise via addition funnel at such a rate so as to maintain the internal reaction temperature below −70° C. After ten min, 1-{4-nitro-3-[(2,2,2-trifluoroethyl)oxy]phenyl}-4-piperidinol (1.83 g, 5.71 mmol) in 8 mL of DMSO and 20 mL of DCM was added dropwise via addition funnel at such a rate so as to maintain the internal reaction temperature below −70° C. The addition funnel was rinsed with 10 mL of DCM, and the reaction was stirred for 1 h. TEA (4.0 mL, 29 mmol) was added dropwise via addition funnel, and the reaction was allowed to warm to rt. The reaction was poured into H2O, and the layers were separated. The aqueous layer was poured into saturated NaHCO3 (aqueous) and extracted with EtOAc. The DCM layer was washed with H2O and brine. The combined organic layers was dried over MgSO4, filtered, and concentrated in vacuo. The crude material was triturated with 2:1 diethyl ether/EtOAc, filtered, and washed with diethyl ether. The yellow solid was collected to afford 1.63 g (90%) of the title compound of step C. 1H NMR (400 MHz, DMSO-d6) δ 7.94 (d, J=9.2 Hz, 1H), 6.70 (dd, J=9.5, 2.6 Hz, 1H), 6.63 (d, J=2.6 Hz, 1H), 4.94 (q, J=8.8 Hz, 2H), 3.82 (t, J=6.0 Hz, 4H), 3.02-3.13 (m, 2H), 1.16 (t, J=7.3 Hz, 2H).

Workup

  1. temperatureto maintain the internal reaction temperature below −70° C
  2. waitAfter ten min
  3. temperatureto maintain the internal reaction temperature below −70° C
  4. washThe addition funnel was rinsed with 10 mL of DCM
  5. stirringthe reaction was stirred for 1 h
  6. customthe layers were separated
  7. additionThe aqueous layer was poured into saturated NaHCO3 (aqueous)
  8. extractionextracted with EtOAc
  9. washThe DCM layer was washed with H2O and brine
  10. dry with materialThe combined organic layers was dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe crude material was triturated with 2:1 diethyl ether/EtOAc
  14. filtrationfiltered
  15. washwashed with diethyl ether
  16. customThe yellow solid was collected

Sources & evidence

ORD record
ord-f19bc9d063d8477e9810e74d7657c2d1
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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