Triphenylphosphine → Methyl 5-fluoro-2-(pent-4-en-2-yloxy)benzoate

HRID 921109Notes

Reaction equation

HRID 921109 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[CH3:13][C@@H:14](O)[CH2:15][CH:16]=[CH2:17].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>C1COCC1.CCOCC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:12][CH:16]([CH2:15][CH:14]=[CH2:13])[CH3:17])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 2783186Methyl 5-fluoro-2-hydroxybenzoateHCID 5363146Diisopropyl azodicarboxylateHCID 6999724(2R)-pent-4-en-2-ol

Product 1

HCID 118307052Methyl 5-fluoro-2-(pent-4-en-2-yloxy)benzoateYield 81%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 5-fluoro-2-hydroxybenzoate (1.0 g, 5.88 mmol), (R)-(−)-pent-4-en-2-ol (1.210 ml, 11.76 mmol) and triphenylphosphine (2.004 g, 7.64 mmol) in THF (14 ml) was added dropwise DIAD (1.486 ml, 7.64 mmol) and the resulting solution was stirred at rt. After 20 h, the reaction was diluted with Et2O and washed with 1N NaOH, water (3×'s) and brine. The organic phase was dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (Biotage; 0%-40% EtOAc/hexane; 20 CV) to give methyl 5-fluoro-2-(pent-4-en-2-yloxy)benzoate (1.1331 g, 4.76 mmol, 81% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.49 (dd, J=8.7, 3.3 Hz, 1H), 7.15 (ddd, J=8.9, 7.7, 3.4 Hz, 1H), 6.96 (dd, J=9.0, 4.2 Hz, 1H), 6.02-5.79 (m, 1H), 5.20-5.06 (m, 2H), 4.50-4.34 (m, 1H), 3.90 (s, 3H), 2.60-2.32 (m, 2H), 1.34 (d, J=6.1 Hz, 3H).

Workup

  1. washwashed with 1N NaOH, water (3×'s) and brine
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography (Biotage; 0%-40% EtOAc/hexane; 20 CV)

Sources & evidence

ORD record
ord-ea84e7e8c279414b964ae8ccbd240ced
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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