Thionyl Chloride → HCID 86722446, compound

HRID 718839Notes

Reaction equation

HRID 718839 reaction equation
O=S(Cl)Cl.[Br:5][C:6]1[C:7]([O:22][CH2:23][CH2:24][C:25]([OH:27])=O)=[CH:8][CH:9]=[C:10]2[C:14]=1[N:13]([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)[N:12]=[CH:11]2.[Cl-].[Al+3].[Cl-].[Cl-]>C(Cl)Cl>[Br:5][C:6]1[C:7]2[O:22][CH2:23][CH2:24][C:25](=[O:27])[C:8]=2[CH:9]=[C:10]2[C:14]=1[N:13]([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)[N:12]=[CH:11]2

Participants

5

Reactant 3

HCID 24386Thionyl Chloride2×HCID 6451240Aluminum(III) ChlorideHCID 86722447HCID 86722447, compound

Product 1

HCID 86722446HCID 86722446, compoundYield 82.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

SOCl2 (4.25 mL, 58.3 mmol) was added dropwise to a slurry of 3-((7-bromo-1-(4-fluorophenyl)-1H-indazol-6-yl)oxy)propanoic acid (98, R1=4-Fluorophenyl) (17.0 g, 44.8 mmol) and DCM (500 mL) under a nitrogen atmosphere at about 0° C. After about 10 min, the ice bath was removed. After about 1 h, SOCl2 (1.00 mL, 13.7 mmol) was added dropwise. After about 3 h, the solution was cooled to 0° C. and then aluminum chloride (18.0 g, 135 mmol) was added in three portions over about 15 min. The ice bath was allowed to thaw to rt over about 2 h. After about 1 h at rt, the mixture was poured into ice water (500 mL). After stirring for about 15 min, the layers were separated and the aqueous layer was extracted with DCM (100 mL). The combined organics were washed with water (100 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was slurried in EtOH (50 mL). The solid was collected by filtration rinsing with EtOH (2×10 mL) then dried under reduced pressure to afford 9-bromo-1-(4-fluorophenyl)-6,7-dihydropyrano[3,2-f]indazol-5(1H)-one (99, R1=4-Fluorophenyl) (13.3 g, 82% yield) as an ivory solid. LC/MS, method 3, Rt=2.26 min, MS m/z 361 and 363 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.50 (s, 1H), 8.42 (s, 1H), 7.61-7.54 (m, 2H), 7.42-7.33 (m, 2H), 4.66 (t, J=6.3 Hz, 2H), 2.89 (t, J=6.3 Hz, 2H).

Workup

  1. customthe ice bath was removed
  2. waitAfter about 1 h
  3. waitAfter about 3 h
  4. customthaw to rt
  5. customover about 2 h
  6. waitAfter about 1 h at rt
  7. customthe layers were separated
  8. extractionthe aqueous layer was extracted with DCM (100 mL)
  9. washThe combined organics were washed with water (100 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. filtrationThe solid was collected by filtration
  14. washrinsing with EtOH (2×10 mL)
  15. customthen dried under reduced pressure

Sources & evidence

ORD record
ord-c36cc4d275ee4e2eaa10b70d935a9f67
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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