Sodium Carbonate → (S)-4-(3,5-dichlorophenyl)-7-({4-[1-hydroxy-1-(trifluoromethyl)propyl]-1H-1,2,3-triazol-1-yl}methyl)quinoline-2-carbonitrile

HRID 2422547Notes

Reaction equation

HRID 2422547 reaction equation
[N+](C1C=CC(C([O:10][C@@:11]([C:18]2[N:19]=[N:20][N:21]([CH2:23][C:24]3[CH:33]=[C:32]4[C:27]([C:28](Cl)=[CH:29][C:30]([C:34]#[N:35])=[N:31]4)=[CH:26][CH:25]=3)[CH:22]=2)([C:14]([F:17])([F:16])[F:15])[CH2:12][CH3:13])=O)=CC=1)([O-])=O.[Cl:39][C:40]1[CH:41]=[C:42](B(O)O)[CH:43]=[C:44]([Cl:46])[CH:45]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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:39][C:40]1[CH:41]=[C:42]([C:28]2[C:27]3[C:32](=[CH:33][C:24]([CH2:23][N:21]4[CH:22]=[C:18]([C@:11]([OH:10])([C:14]([F:16])([F:17])[F:15])[CH2:12][CH3:13])[N:19]=[N:20]4)=[CH:25][CH:26]=3)[N:31]=[C:30]([C:34]#[N:35])[CH:29]=2)[CH:43]=[C:44]([Cl:46])[CH:45]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343313,5-Dichlorophenylboronic acidHCID 66790930(S)-1-{1-[(4-chloro-2-cyanoquinolin-7-yl)methyl]-1H-1,2,3-triazol-4-yl}-1-(trifluoromethyl)propyl 4-nitrobenzoate

Product 1

HCID 66790617(S)-4-(3,5-dichlorophenyl)-7-({4-[1-hydroxy-1-(trifluoromethyl)propyl]-1H-1,2,3-triazol-1-yl}methyl)quinoline-2-carbonitrile

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of (S)-1-{1-[(4-chloro-2-cyanoquinolin-7-yl)methyl]-1H-1,2,3-triazol-4-yl}-1-(trifluoromethyl)propyl 4-nitrobenzoate (150 mg, 0.28 mmol) in DME (3 mL) was added tetrakis(triphenylphosphine)palladium (16 mg, 0.014 mmol), 3,5-dichlorophenylboronic acid (80 mg, 0.42 mmol) and aq. 2M Na2CO3 (0.42 mL, 0.84 mmol). After 1.5 h at 100° C., the reaction was quenched with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduce pressure. To this crude product was added THF (4 mL) and LiOH IM (1.4 mL, 1.4 mmol). After 2 h at rt, the reaction was quenched with saturated aqueous NH4Cl and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduce pressure. Purification on silica gel (eluting with EtOAc/hexanes, 3:7) gave the title compound. MS (+ESI): 506 (M+H)+.

Workup

  1. customthe reaction was quenched with water
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionTo this crude product was added THF (4 mL) and LiOH IM (1.4 mL, 1.4 mmol)
  8. waitAfter 2 h at rt
  9. customthe reaction was quenched with saturated aqueous NH4Cl
  10. extractionextracted with EtOAc
  11. washThe combined organic layers were washed with brine
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customPurification on silica gel (eluting with EtOAc/hexanes, 3:7)

Sources & evidence

ORD record
ord-663ba5a2f9724428967606fe9ea0a9d9
Source dataset
uspto-grants-2011_06
Patent number
US07960409B2

Reaction notes

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