Benzyl Alcohol → Methyl 3-(benzyloxy)-4-nitrobenzoate

HRID 1505829Notes

Reaction equation

HRID 1505829 reaction equation
[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[C:6]([OH:13])[CH:5]=1.[CH2:15](O)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.CC[NH+](CC)CC.CC[NH+](CC)CC.C([O-])([O-])=O>C1COCC1.C(Cl)Cl>[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[C:6]([O:13][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:5]=1

Participants

8

Reactant 5

HCID 244Benzyl AlcoholHCID 11776TriphenylphosphineHCID 294866Methyl 3-hydroxy-4-nitrobenzoateHCID 5363146Diisopropyl azodicarboxylateHCID 15264167Carbonic acid--N,N-diethylethanamine (1/2)

Product 1

HCID 15054012Methyl 3-(benzyloxy)-4-nitrobenzoateYield 94%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl-3-hydroxy-4-nitrobenzoate Cmpd 1 (1.0 g, 1.0 eq) was dissolved in THF (6 mL) in a microwave vial. Benzyl alcohol (1.0 eq) and PPh3 (1.0 eq) were added to the vial. The reaction vial was put under nitrogen flow, and DIAD (1.0 eq) was added in the dark after stirring the reaction for 1.5 hours. The reaction was microwave irradiated at 100° C. for 6 min (Biotage Initiator™ Eight). The solution was concentrated, and purification of the resultant was performed on a SP1 flash chromatography system (Biotage™) starting with 6% EtOAc: 94% Hex to 60% EtOAc: 40% Hex. The recovered yellow solid was treated with MP-Carbonate resin (2 eq) in DCM and the mixture was shaken overnight at RT. The resin was filtered and multiply washed with DCM. The filtrate was concentrated under vacuum to give Cmpd 2 as a yellow solid (1.39 g, 94% yield).

Workup

  1. customThe reaction
  2. additionwas added in the dark
  3. customthe reaction for 1.5 hours
  4. customThe reaction was microwave irradiated at 100° C. for 6 min (Biotage Initiator™ Eight)
  5. concentrationThe solution was concentrated
  6. custompurification of the resultant
  7. stirringthe mixture was shaken overnight at RT
  8. filtrationThe resin was filtered
  9. washmultiply washed with DCM
  10. concentrationThe filtrate was concentrated under vacuum

Sources & evidence

ORD record
ord-5288109716384962883d137844aba3c2
Source dataset
uspto-grants-2015_12
Patent number
US09217022B2

Reaction notes

Loading…