Benzyl 4-Hydroxybenzoate → (R)-benzyl 4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)benzoate

HRID 1172939Notes

Reaction equation

HRID 1172939 reaction equation
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.[OH:34][C:35]1[CH:50]=[CH:49][C:38]([C:39]([O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[O:40])=[CH:37][CH:36]=1.[CH3:51][C:52]1([CH3:59])[O:56][C@H:55]([CH2:57]O)[CH2:54][O:53]1>C1COCC1.CCOCC.CCCCCCC>[CH3:51][C:52]1([CH3:59])[O:56][C@H:55]([CH2:57][O:34][C:35]2[CH:50]=[CH:49][C:38]([C:39]([O:41][CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[O:40])=[CH:37][CH:36]=2)[CH2:54][O:53]1

Participants

8

Reactant 4

HCID 7180Benzyl 4-HydroxybenzoateHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 736056(R)-Solketal

Product 1

HCID 59556712(R)-benzyl 4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)benzoateYield 100%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8900HeptaneSolvent

Conditions

Temperature
0 °C

Procedure

In a 250 mL round-bottomed flask was added triphenylphosphine (6.54 g, 24.92 mmol) in THF (79 ml) to give a colorless clear solution. The solution was cooled to 0° C. by ice-bath. After stirring for 15 min, diisopropyl azodicarboxylate (5.11 ml, 24.96 mmol) (orange liquid) was added dropwise over 5 min. The reaction mixture turned into off-white suspension in the process. The reaction mixture was stirred at 0° C. for 30 min. Then a colorless solution of benzyl 4-hydroxybenzoate (5.69 g, 24.92 mmol) and (R)-(2,2-dimethyl-1,3-dioxolan-4-yl)methanol (3.00 ml, 23.73 mmol) in THF (39.5 ml) was added to the mixture, keeping the temperature at or below 0° C. The solution turned clear light yellow. The solution was stirred for 2 hr at 0° C. then slowly warmed to ambient temperature and stirred over the weekend. The mixture was concentrated in vacuo to give crude yellow oil (˜27 g). The crude oil was dissolved in ether. Then heptane was added. The resultant precipitate was sonicated and filtered. The filtrate was concentrated and purified via Analogix system using RediSep RS 120 g column, with a gradient of 0-20% EtOAc/Heptane over 10 min at 50 mL/min then hold at 20% ethyl acetate for 20 min. Fractions containing product were combined and concentrated to afford (R)-benzyl 4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)benzoate as white solid (6.17 g, 23.73 mmol). LCMS (Table 1, Method c) Rt=2.89 min, m/z 343.20 (M+H)+

Workup

  1. customto give a colorless clear solution
  2. stirringThe reaction mixture was stirred at 0° C. for 30 min
  3. custombelow 0° C
  4. stirringThe solution was stirred for 2 hr at 0° C.
  5. temperaturethen slowly warmed to ambient temperature
  6. stirringstirred over the weekend
  7. concentrationThe mixture was concentrated in vacuo
  8. customto give crude yellow oil (˜27 g)
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated
  11. custompurified via Analogix system
  12. waitwith a gradient of 0-20% EtOAc/Heptane over 10 min at 50 mL/min then hold at 20% ethyl acetate for 20 min
  13. additionFractions containing product
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-016e3c795add47f488cded79ac0c278c
Source dataset
uspto-grants-2010_11
Patent number
US07834039B2

Reaction notes

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