Triphenylphosphine → HCID 59310145, compound

HRID 1513008Notes

Reaction equation

HRID 1513008 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][O:11][C:12]1[C:17]([CH2:18][OH:19])=[C:16]([F:20])[C:15]([F:21])=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:22][C:23]1[CH:28]=[CH:27][C:26](O)=[CH:25][C:24]=1[N+:30]([O-])=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C(=O)([O-])O.[Na+]>O1CCCC1>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][O:11][C:12]1[C:17]([CH2:18][O:19][C:26]2[CH:27]=[CH:28][C:23]([Cl:22])=[C:24]([CH:25]=2)[NH2:30])=[C:16]([F:20])[C:15]([F:21])=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 11776TriphenylphosphineHCID 691274-Chloro-3-nitrophenolHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 516892Sodium BicarbonateHCID 59309832HCID 59309832, compound

Product 1

HCID 59310145HCID 59310145, compoundYield 98.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-[2-(tert-butoxycarbonylamino)ethoxy]-2,3-difluorobenzyl alcohol (0.54 g), 4-chloro-3-nitrophenol (0.31 g) and triphenylphosphine (0.54 g) in tetrahydrofuran (4 mL) was added diisopropyl azodicarboxylate (40% toluene solution, 1.03 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was dissolved in tetrahydrofuran (6 mL). To the solution were added methanol (6 mL) and nickel(II) bromide (20 mg). To the mixture was added sodium borohydride (0.2 g) under ice-cooling, and the mixture was stirred at the same temperature for 30 minutes, and then stirred at room temperature for 30 minutes. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, and the resulting mixture was extracted with ethyl acetate. The extract was washed with brine twice, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/1−1/1) and column chromatography on amino-propylated silica gel (eluent: n-hexane/ethyl acetate=3/1−2/3) successively to give the title compound (0.75 g).

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate
  2. washThe extract was washed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. dissolutionthe residue was dissolved in tetrahydrofuran (6 mL)
  6. additionTo the solution were added methanol (6 mL) and nickel(II) bromide (20 mg)
  7. additionTo the mixture was added sodium borohydride (0.2 g) under ice-
  8. temperaturecooling
  9. stirringthe mixture was stirred at the same temperature for 30 minutes
  10. stirringstirred at room temperature for 30 minutes
  11. additionThe reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution
  12. extractionthe resulting mixture was extracted with ethyl acetate
  13. washThe extract was washed with brine twice
  14. dry with materialdried over anhydrous magnesium sulfate
  15. customThe solvent was removed under reduced pressure
  16. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/1−1/1) and column chromatography on amino-propylated silica gel (eluent: n-hexane/ethyl acetate=3/1−2/3) successively

Sources & evidence

ORD record
ord-b65862ab635b4f578841cdf8de7eaed7
Source dataset
uspto-grants-2012_07
Patent number
US08217069B2

Reaction notes

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