Hydrochloric Acid → 4-Chloro-3',5'-difluoro-6-(1-hydroxyethyl)-3-methylbiphenyl-2-carbaldehyde

HRID 1499723Notes

Reaction equation

HRID 1499723 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([Cl:21])[C:7]([CH3:20])=[C:8]([C:18]#N)[C:9]=1[C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=1)(=[O:3])[CH3:2].[H-].C([Al+]CC(C)C)C(C)C.CCCCCC.Cl.[OH2:39]>C(Cl)Cl>[Cl:21][C:6]1[C:7]([CH3:20])=[C:8]([CH:18]=[O:39])[C:9]([C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=2)=[C:4]([CH:1]([OH:3])[CH3:2])[CH:5]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 8058HexaneHCID 21225700DiisobutylaluminumhydrideHCID 866667936-Acetyl-4-chloro-3',5'-difluoro-3-methylbiphenyl-2-carbonitrile

Product 1

HCID 866776594-Chloro-3',5'-difluoro-6-(1-hydroxyethyl)-3-methylbiphenyl-2-carbaldehydeYield 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 6-acetyl-4-chloro-3′,5′-difluoro-3-methylbiphenyl-2-carbonitrile (2.43 g, 7.95 mmol) in methylene chloride (50 mL) was added 1.0 M diisobutylaluminum hydride in hexane (19.9 mL, 19.9 mmol) at −78° C. The reaction was warmed to rt over 2 h with stirring. 5.0 M Hydrogen chloride in water (70 mL) was added slowly, and stirring was continued for 1 h. The resultant mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate and then concentrated to dry. The residue was purified on silica gel, eluting with 0 to 50% EtOAc in hexanes, to give the desired product (2.4 g, 97%). LCMS calculated for C16H12ClF2O (M-OH)+: m/z=293.1; Found: 293.1.

Workup

  1. stirringstirring
  2. extractionThe resultant mixture was extracted with EtOAc
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customto dry
  7. customThe residue was purified on silica gel
  8. washeluting with 0 to 50% EtOAc in hexanes

Sources & evidence

ORD record
ord-baf6d614c76d4b05900fd6804423cdc9
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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