Methanol → HCID 118184923, compound

HRID 2177412Notes

Reaction equation

HRID 2177412 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[CH:20]=[CH:19][C:18](/[CH:21]=[CH:22]/[C:23]([O:25][CH3:26])=[O:24])=[C:17]([CH:27]([F:29])[F:28])[CH:16]=3)=[C:11]([C:30]([F:33])([F:32])[F:31])[S:10][N:9]=2)=[CH:4][CH:3]=1.CO.[BH4-].[Na+]>[Ni](Cl)Cl.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][C:23]([O:25][CH3:26])=[O:24])=[C:17]([CH:27]([F:28])[F:29])[CH:16]=3)=[C:11]([C:30]([F:32])([F:31])[F:33])[S:10][N:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 118363333HCID 118363333, compound

Product 1

HCID 118184923HCID 118184923, compoundYield 54.4%

Reagents, catalysts & solvents 2

HCID 24385Nickel DichlorideCatalystHCID 962WaterSolvent

Procedure

(E)-Methyl 3-(4-((3-(4-chlorophenyl)-5-(trifluoromethyl)isothiazol-4-yl)methoxy)-2-(difluoromethyl)phenyl)acrylate (55 mg, 0.109 mmol) in a mixed solvent system (MeOH (2 mL); water (0.5 mL)) was treated with sodium borohydride (8.2 mg, 0.218 mmol) and nickel chloride (1.5 mg, 0.011 mmol) for 10 min. The solvent was removed and the residue was partitioned between ethyl acetate and saturated ammonium chloride. The organic layer was dried, filtered, and the filtrate was concentrated under reduced pressure. The resultant residue was concentrated and purified by prep-HPLC, eluting with 20-80% acetonitrile in water (0.5% TFA) to give compound 267d as a white solid (30 mg, 54% yield).

Workup

  1. customThe solvent was removed
  2. customthe residue was partitioned between ethyl acetate and saturated ammonium chloride
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. concentrationThe resultant residue was concentrated
  7. custompurified by prep-HPLC,
  8. washeluting with 20-80% acetonitrile in water (0.5% TFA)

Sources & evidence

ORD record
ord-e971fa36d85a433a9d2c2e0c9ea2d697
Source dataset
uspto-grants-2015_06
Patent number
US09067898B1

Reaction notes

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