Di-tert-butyl dicarbonate → HCID 59458401, compound

HRID 1874201Notes

Reaction equation

HRID 1874201 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:7]([C:10](=[O:25])[C:11]2[CH:16]=[C:15]([O:17][C:18]([F:23])([F:22])[CH:19]([F:21])[F:20])[CH:14]=[C:13]([F:24])[CH:12]=2)=[CH:6][C:3]=1[C:4]#[N:5].[O:26](C(OC(C)(C)C)=O)[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=O.[BH4-].[Na+]>CO.[Ni](Cl)Cl>[F:1][C:2]1[CH:9]=[CH:8][C:7]([CH:10]([C:11]2[CH:16]=[C:15]([O:17][C:18]([F:23])([F:22])[CH:19]([F:20])[F:21])[CH:14]=[C:13]([F:24])[CH:12]=2)[OH:25])=[CH:6][C:3]=1[CH2:4][NH:5][C:27](=[O:26])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31]

Participants

6

Reactant 3

HCID 90495Di-tert-butyl dicarbonateHCID 4311764Sodium borohydrideHCID 59458590HCID 59458590, compound

Product 1

HCID 59458401HCID 59458401, compound

Reagents, catalysts & solvents 2

HCID 24385Nickel DichlorideCatalystHCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-fluoro-5-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzoyl)benzonitrile (1.30 g, 3.62 mmol), BOC2O (1.68 mL, 7.24 mmol) and Nickel (II) chloride (0.47 g, 3.62 mmol) in MeOH at 0° C. was added sodium borohydride (0.96 g, 25.3 mmol). The reaction mixture was stirred at 0° C. for 30 minutes and then at room temperature for 6 h. The reaction mixture was filtered through celite and the filtrate was concentrated. The residue was diluted with EtOAc and the solution was washed with sat. NaHCO3. The organic layer was dried over Na2SO4, filtered and concentrated to yield tert-butyl 2-fluoro-5-((3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)(hydroxy)methyl)benzylcarbamate as a clear, colorless oil (1.43 g, 85% yield). This product was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 7.32 (m, 1H), 7.22 (m, 1H), 7.03 (m, 3H),), 6.87 (d, J=8.84 Hz, 1H), 5.90 (m, 2H), 4.98 (br. s., 1H), 4.31 (d, J=5.05 Hz, 2H).

Workup

  1. waitat room temperature for 6 h
  2. filtrationThe reaction mixture was filtered through celite
  3. concentrationthe filtrate was concentrated
  4. additionThe residue was diluted with EtOAc
  5. washthe solution was washed with sat. NaHCO3
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-beda67b7b28b4b389d49b3f2d9c9f53d
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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