Benzyl Alcohol → HCID 86619290, compound

HRID 1362896Notes

Reaction equation

HRID 1362896 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:19]=[C:18]([F:20])[C:17]([F:21])=[CH:16][C:15]=2[F:22])[C@@H:10](C(O)=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:28]([CH2:31]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:40])C=CC=CC=1.[CH2:50]([OH:57])[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1>C1(C)C=CC=CC=1>[CH2:50]([O:57][C:31]([NH:28][C@@H:10]1[C@@H:11]([C:14]2[CH:19]=[C:18]([F:20])[C:17]([F:21])=[CH:16][C:15]=2[F:22])[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]1)=[O:40])[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 66962521HCID 66962521, compound

Product 1

HCID 86619290HCID 86619290, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To 2.8 g (7.8 mmol) of the product of Step C in 50 mL of toluene was added 1.3 mL (9.0 mmol) of triethylamine followed by 1.9 mL (9.0 mmol) of diphenylphosphoryl azide. After stirring at ambient temperature for 30 min, the reaction mixture was warmed to 70° C. for 30 min then slowly heated to reflux for an additional 2 h. The reaction mixture was then cooled to ambient temperature and 2.4 mL (22 mmol) of benzyl alcohol was added. The reaction mixture was heated to reflux for 5 h then cooled to ambient temperature and quenched with 1N aqueous hydrochloric acid (100 mL). The resulting mixture was extracted with three 150-mL portions of ethyl acetate, and the organic phases combined and washed sequentially with 1N hydrochloric acid, saturated aqueous sodium bicarbonate solution, and saturated aqueous brine (70 mL each). The organic phase was then dried over magnesium sulfate, filtered, and evaporated in vacuo to yield a viscous crude oil which was purified by flash chromatography on a Biotage Horizon® system (silica gel, 0 to 30% ethyl acetate/hexanes gradient) to give the title compound as a viscous oil. LC/MS 365.3 (M-Boc).

Workup

  1. temperaturethe reaction mixture was warmed to 70° C. for 30 min
  2. temperaturethen slowly heated
  3. temperatureto reflux for an additional 2 h
  4. temperatureThe reaction mixture was then cooled to ambient temperature
  5. temperatureThe reaction mixture was heated
  6. temperatureto reflux for 5 h
  7. temperaturethen cooled to ambient temperature
  8. customquenched with 1N aqueous hydrochloric acid (100 mL)
  9. extractionThe resulting mixture was extracted with three 150-mL portions of ethyl acetate
  10. washwashed sequentially with 1N hydrochloric acid, saturated aqueous sodium bicarbonate solution, and saturated aqueous brine (70 mL each)
  11. dry with materialThe organic phase was then dried over magnesium sulfate
  12. filtrationfiltered
  13. customevaporated in vacuo
  14. customto yield a viscous crude oil which
  15. customwas purified by flash chromatography on a Biotage Horizon® system (silica gel, 0 to 30% ethyl acetate/hexanes gradient)

Sources & evidence

ORD record
ord-0ec8a5ddb43649269023633a2cb58221
Source dataset
uspto-grants-2011_02
Patent number
US07884104B2

Reaction notes

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