Water → 3',5'-Dichloro-4'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-4-fluoro-biphenyl-3-carbonitrile

HRID 2235334Notes

Reaction equation

HRID 2235334 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[C:11]([Cl:13])[C:10]([CH2:14][CH:15]2[CH2:19][CH2:18][N:17]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)[C:16]2=[O:26])=[C:9]([Cl:27])[CH:8]=1)(=O)=O.[C:30]([C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][C:37]=1[F:38])#[N:31].C(=O)([O-])[O-].[Na+].[Na+].O>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:13][C:11]1[CH:12]=[C:7]([C:34]2[CH:35]=[CH:36][C:37]([F:38])=[C:32]([C:30]#[N:31])[CH:33]=2)[CH:8]=[C:9]([Cl:27])[C:10]=1[CH2:14][CH:15]1[CH2:19][CH2:18][N:17]([CH:20]2[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]2)[C:16]1=[O:26]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27579643-Cyano-4-fluorophenylboronic acidHCID 592994213,5-Dichloro-4-((1-cyclohexyl-2-oxopyrrolidin-3-yl)methyl)phenyl trifluoromethanesulfonate

Product 1

HCID 592995283',5'-Dichloro-4'-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-4-fluoro-biphenyl-3-carbonitrileYield 88%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 3,5-dichloro-4-((1-cyclohexyl-2-oxopyrrolidin-3-yl)methyl)phenyl trifluoromethanesulfonate (Example 240) (1.34 g, 2.83 mmol) in THF (30 mL) in a round bottom flask was added 3-cyano-4-fluorophenylboronic acid (560 mg, 3.39 mmol), sodium carbonate (900 mg, 8.48 mmol) and water (10 mL). The mixture was stirred at 60° C. for 5 minutes, palladium tetrakis (163 mg, 0.14 mmol) was added. Reaction mixture was brought to 80° C. and stirred for 3 hours. Cooled and partitioned between ethyl acetate and HCL(1 N). Organic was separated, wash with water, brine; dry over sodium sulfate, filter, and concentrate. Purify by silica gel (25-50% ethyl acetate in hexane) to afford 1.10 g (88%) of the title compound: Mass spectrum (LCMS) m/z=445.0 (M+H).

Workup

  1. customReaction mixture
  2. customwas brought to 80° C.
  3. stirringstirred for 3 hours
  4. temperatureCooled
  5. custompartitioned between ethyl acetate and HCL(1 N)
  6. customOrganic was separated
  7. washwash with water, brine
  8. dry with materialdry over sodium sulfate
  9. filtrationfilter
  10. concentrationconcentrate
  11. customPurify by silica gel (25-50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-947db249f38c44959a558af280c17a6a
Source dataset
uspto-grants-2010_05
Patent number
US07713979B2

Reaction notes

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