Triphenylphosphine → HCID 22010521, compound

HRID 322967Notes

Reaction equation

HRID 322967 reaction equation
N(C(OC(C)C)=O)=NC(OC(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:34][C:35]1[CH:42]=[C:41]([OH:43])[CH:40]=[CH:39][C:36]=1[C:37]#[N:38].O[CH2:45][C:46]1[CH:47]=[C:48]([CH2:52][CH2:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH:49]=[CH:50][CH:51]=1>O1CCCC1>[C:37]([C:36]1[CH:39]=[CH:40][C:41]([O:43][CH2:45][C:46]2[CH:47]=[C:48]([CH2:52][CH2:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH:49]=[CH:50][CH:51]=2)=[CH:42][C:35]=1[F:34])#[N:38]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 27346752-Fluoro-4-hydroxybenzonitrileHCID 22010136HCID 22010136, compound

Product 1

HCID 22010521HCID 22010521, compoundYield 13.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Diisopropyl azodicarboxylate (2.6 g) is added portionwise to a stirred solution of triphenylphosphine (3.4 g) in dry tetrahydrofuran (40 mL) at 0° C. under nitrogen. The reaction mixture is stirred at 0° C. for 15 minutes then treated with a solution of 2-fluoro-4-hydroxybenzonitrile (0.87 g) and t-butyl 3-(3-hydroxymethylphenyl)propionate (1.5 g) in dry tetrahydrofuran (10 mL) whilst maintaining the temperature at 0-5° C. Stirring is continued at this temperature for 1 hour when the reaction mixture is allowed to warm up to room temperature. The reaction mixture is evaporated to low bulk and partitioned between ethyl acetate (100 mL) and water (100 mL). The organic phase is washed with water (50 mL), dried over magnesium sulphate and evaporated. The residue is purified by flash chromatography on silica eluting with a mixture of cyclohexane and ethyl acetate (4:1 v/v). Fractions homogeneous in the required product are combined and evaporated to give tert-butyl 3-[3-(4-cyano-3-fluoro-phenoxymethyl)phenyl]propionate (0.3 g).

Workup

  1. temperaturewhilst maintaining the temperature at 0-5° C
  2. stirringStirring
  3. waitis continued at this temperature for 1 hour
  4. temperatureto warm up to room temperature
  5. customThe reaction mixture is evaporated to low bulk
  6. custompartitioned between ethyl acetate (100 mL) and water (100 mL)
  7. washThe organic phase is washed with water (50 mL)
  8. dry with materialdried over magnesium sulphate
  9. customevaporated
  10. customThe residue is purified by flash chromatography on silica eluting with a mixture of cyclohexane and ethyl acetate (4:1 v/v)
  11. customevaporated

Sources & evidence

ORD record
ord-b17fb1428906487687abb46ac1798e6f
Source dataset
uspto-grants-2001_04
Patent number
US06211234B1

Reaction notes

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