Benzyl Alcohol → HCID 86635031, compound

HRID 908500Notes

Reaction equation

HRID 908500 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]2[C:13](=[O:14])[CH2:12][C@@H:11]([C:15]3[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=3[F:23])[C@H:10](C(O)=O)[CH2:9]2)=[CH:5][CH:4]=1.C([N:31]([CH2:34]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:43])C=CC=CC=1.[CH2:53]([OH:60])[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]2[C:13](=[O:14])[CH2:12][C@@H:11]([C:15]3[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=3[F:23])[C@H:10]([NH:31][C:34](=[O:43])[O:60][CH2:53][C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[CH2:9]2)=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 66790702HCID 66790702, compound

Product 1

HCID 86635031HCID 86635031, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
50 °C

Procedure

To 26.3 g (66.8 mmol) of the product of Step E in 500 mL of toluene was added 12.2 nm (86.9 mmol) of triethylamine followed by 18.8 mL (86.9 mmol) of diphenylphosphoryl azide. The slurry was slowly heated to 50° C. over 30 min then to 70° C. over 20 min and held at this temperature for an additional 20 min. The clear brown solution was then heated to reflux over a period of 40 min and stirred at this temperature for an additional 3 h. The reaction mixture was cooled to ambient temperature, 20.8 mL (200.5 mmol) of benzyl alcohol was added, and the reaction mixture was heated to reflux for 3 h. The reaction was cooled to 100° C., stirred for an additional 14 h, then cooled to ambient temperature, and concentrated. The residue was stirred for 5 min in 100 mL of ethyl acetate and filtered to provide the first crop of the title compound. The filtrate was poured into a mixture of 1N aqueous hydrochloric acid (500 mL) and ethyl acetate (250 mL). The resulting mixture was extracted with three 150-mL portions of ethyl acetate, the organic phases combined and washed sequentially with 1N hydrochloric acid, saturated aqueous sodium bicarbonate solution, and saturated aqueous brine (100 mL each). The organic phase was then dried over magnesium sulfate, filtered, and evaporated in vacuo to yield a viscous crude oil. The remaining crude material was purified by flash chromatography on a Biotage Horizon® system (silica gel, 0 to 80% ethyl acetate/hexanes gradient) to give the title compound as a white crystalline solid. LC/MS 499.0 (M+1).

Workup

  1. waitheld at this temperature for an additional 20 min
  2. temperatureThe clear brown solution was then heated
  3. temperatureto reflux over a period of 40 min
  4. temperatureThe reaction mixture was cooled to ambient temperature
  5. temperaturethe reaction mixture was heated
  6. temperatureto reflux for 3 h
  7. temperatureThe reaction was cooled to 100° C.
  8. stirringstirred for an additional 14 h
  9. temperaturecooled to ambient temperature
  10. concentrationconcentrated
  11. stirringThe residue was stirred for 5 min in 100 mL of ethyl acetate
  12. filtrationfiltered

Sources & evidence

ORD record
ord-36703a1ec00048d890080c283fe93bd7
Source dataset
uspto-grants-2011_09
Patent number
US08017624B2

Reaction notes

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