Hydrochloric Acid → HCID 58689910, compound

HRID 2250948Notes

Reaction equation

HRID 2250948 reaction equation
[CH:1]([NH:4][NH:5][C:6](=[O:16])[C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-])=O)=[CH:9][CH:8]=1)([CH3:3])[CH3:2].[F:17][C:18]1[CH:19]=[CH:20][C:21]([O:35][CH2:36][C:37]([OH:39])=O)=[C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[O:30][C:31]([F:34])([F:33])[F:32])[CH:23]=1.CCN(C(C)C)C(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.Cl.[CH:74](=O)[CH:75]([CH3:77])[CH3:76]>CN(C=O)C.C(OCC)(=O)C.CCO.C(O)(=O)C.[Pd]>[F:17][C:18]1[CH:19]=[CH:20][C:21]([O:35][CH2:36][C:37]([N:4]([CH:1]([CH3:3])[CH3:2])[NH:5][C:6](=[O:16])[C:7]2[CH:12]=[CH:11][C:10]([NH:13][CH2:74][CH:75]([CH3:77])[CH3:76])=[CH:9][CH:8]=2)=[O:39])=[C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[O:30][C:31]([F:34])([F:33])[F:32])[CH:23]=1

Participants

12

Reactant 6

HCID 313Hydrochloric AcidHCID 6561IsobutyraldehydeHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 12170553HCID 12170553, compoundHCID 58689904(5-Fluoro-2'-trifluoromethoxy-biphenyl-2-yloxy)-acetic acid

Product 1

HCID 58689910HCID 58689910, compoundYield 39%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidCatalystHCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 4-nitro-benzoic acid N′-isopropyl-hydrazide (84 mg, 0.378 mmol), (5-fluoro-2′-trifluoromethoxy-biphenyl-2-yloxy)-acetic acid (100 mg, 0.302 mmol), and DIPEA (0.329 ml, 1.89 mmol) in DMF (5 ml) was treated with PyBroP (176 mg, 0.378 mmol) and let stir at 25° C. overnight. The reaction mixture was diluted with 70 ml ethyl acetate and extracted with 1N HCl (2×30 ml), saturated sodium bicarbonate (2×30 ml). The organic layer was dried over sodium sulfate, filtered, and concentrated to a gum (150 mg). The crude material (75 mg, 0.14 mmol) dissolved in EtOH (5 ml) containing acetic acid (2 drops), concentrated HCl (20 μl), isobutyraldehyde (152 μl, 1.68 mmol) and 10% palladium on carbon (10 mg) This mixture was hydrogenated at 20 psi at rt for 5 hours. The reaction mixture was filtered through celite diluted with ethyl acetate, washed with saturated sodium bicarbonate, dried over sodium sulfate, filtered and concentrated. The crude product was triturated with 1% ethyl acetate/hexanes to give an off-white solid (31 mg, 39%). MS m/e 562 (M+H+)

Workup

  1. extractionextracted with 1N HCl (2×30 ml), saturated sodium bicarbonate (2×30 ml)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated to a gum (150 mg)
  5. waitwas hydrogenated at 20 psi at rt for 5 hours
  6. filtrationThe reaction mixture was filtered through celite
  7. additiondiluted with ethyl acetate
  8. washwashed with saturated sodium bicarbonate
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product was triturated with 1% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-f0fd546268bc473cb4084405f04adcfd
Source dataset
uspto-grants-2008_01
Patent number
US07317125B2

Reaction notes

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