Triphenylphosphine → HCID 86609533, compound

HRID 2263603Notes

Reaction equation

HRID 2263603 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[Cl:34][C:35]1[CH:55]=[C:54]([Cl:56])[CH:53]=[CH:52][C:36]=1[C:37]([NH:39][CH2:40][C:41]1([CH2:48][CH:49]2[CH2:51][CH2:50]2)[CH2:46][CH2:45][CH:44]([OH:47])[CH2:43][CH2:42]1)=[O:38].[C:57](O)(=[S:59])[CH3:58].C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[CH:49]1([CH2:48][C:41]2([CH2:40][NH:39][C:37](=[O:38])[C:36]3[CH:52]=[CH:53][C:54]([Cl:56])=[CH:55][C:35]=3[Cl:34])[CH2:42][CH2:43][CH:44]([O:47][C:57](=[S:59])[CH3:58])[CH2:45][CH2:46]2)[CH2:51][CH2:50]1

Participants

7

Reactant 5

HCID 11776Triphenylphosphine2×HCID 13097Triphenylphosphine OxideHCID 5363146Diisopropyl azodicarboxylateHCID 68682722HCID 68682722, compoundHCID 178418634HCID 178418634, compound

Product 1

HCID 86609533HCID 86609533, compoundYield 63.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of triphenylphosphine (0.44 g; 1.68 mmol) in THF (20 ml) at 0° C. was added diisopropylazodicarboxylate (0.34 g; 1.68 mmol) and the solution stirred at 0° C. for 90 minutes. To a stirred solution of 2,4-dichloro-N-{[1-(cyclopropylmethyl)-4-hydroxycyclohexyl]methyl}benzamide (0.30 g; 0.84 mmol; less polar alcohol isomer) in THF (10 ml) was added thioacetic acid (0.12 ml; 1.68 mmol). The resulting solution was added dropwise to the triphenylphosphine solution at 0° C. On complete addition, the solution was stirred at 0° C. for 1 hour then allowed to warm to ambient temperature and stirred for 18 hours. The reaction mixture was partitioned between EtOAc (200 ml) and water (100 ml). The organic phase was washed with brine (100 ml), dried over anhydrous sodium sulfate, filtered and evaporated to give a yellow oily solid. The crude product was chromatographed on silica eluted with 10-30% EtOAc in isohexane to give the product contaminated with triphenylphosphine oxide. The contaminated product was chromatographed on silica eluted with 1% EtOAc in dichloromethane to give the desired product as an oil (220 mg). 1H NMR δ (ppm) (CDCl3): 7.66 (1H, d, J=8.4 Hz), 7.43 (1H, d, J=2.1 Hz), 7.34 (1H, dd, J=2.1, 8.4 Hz), 6.26 (1H, s), 3.58 (2H, d, J=6.0 Hz), 3.45-3.52 (1H, m), 2.30 (3H, s), 1.83-1.88 (2H, m), 1.65-1.74 (4H, m), 1.44-1.52 (2H, m), 1.26 (2H, d, J=7.0 Hz), 0.64-0.71 (1H, m), 0.47-0.52 (2H, m), 0.00-0.06 (2H, m).

Workup

  1. additionOn complete addition
  2. stirringthe solution was stirred at 0° C. for 1 hour
  3. temperatureto warm to ambient temperature
  4. stirringstirred for 18 hours
  5. customThe reaction mixture was partitioned between EtOAc (200 ml) and water (100 ml)
  6. washThe organic phase was washed with brine (100 ml)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customto give a yellow oily solid
  11. customThe crude product was chromatographed on silica
  12. washeluted with 10-30% EtOAc in isohexane
  13. customto give the product
  14. customThe contaminated product was chromatographed on silica
  15. washeluted with 1% EtOAc in dichloromethane

Sources & evidence

ORD record
ord-00b3c6043ee144b4bf228f9f2caf8886
Source dataset
uspto-grants-2010_12
Patent number
US07851638B2

Reaction notes

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