Triphenylphosphine → (S)-2,4-difluoro-6-(pent-4-en-2-yloxy)benzaldehyde

HRID 921124

Reaction equation

HRID 921124 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[C:6]([OH:11])[C:3]=1[CH:4]=[O:5].[CH3:12][C@@H:13](O)[CH2:14][CH:15]=[CH2:16].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:9]=[C:8]([F:10])[CH:7]=[C:6]([O:11][C@H:15]([CH2:14][CH:13]=[CH2:12])[CH3:16])[C:3]=1[CH:4]=[O:5]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 6999724(2R)-pent-4-en-2-olHCID 225079192,4-Difluoro-6-hydroxybenzaldehyde

Product 1

HCID 118307036(S)-2,4-difluoro-6-(pent-4-en-2-yloxy)benzaldehydeYield 23.72%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2,4-difluoro-6-hydroxybenzaldehyde (1.0 g, 6.33 mmol) in THF (14 ml) were added (R)-(−)-pent-4-en-2-ol (1.090 g, 12.65 mmol) and triphenylphosphine (2.157 g, 8.22 mmol). To this mixture was added dropwise DIAD (1.599 ml, 8.22 mmol) (exotherm) and stirred at rt. After 20 h, the mixture was diluted with Et2O and washed with 1N NaOH followed by water (3×'s) then brine, dried (Na2SO4), filtered and concentrated. The crude was purified by flash chromatography (Biotage; 0%-50% EtOAc/hexane; 10 CV) to give (S)-2,4-difluoro-6-(pent-4-en-2-yloxy)benzaldehyde (0.3394 g, 1.500 mmol, 23.72% yield) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ: 10.33 (s, 1H), 6.67-6.32 (m, 2H), 6.04-5.63 (m, 1H), 5.32-5.00 (m, 2H), 4.66-4.40 (m, 1H), 2.68-2.28 (m, 2H), 1.41 (d, J=6.1 Hz, 3H).

Workup

  1. washwashed with 1N NaOH
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude was purified by flash chromatography (Biotage; 0%-50% EtOAc/hexane; 10 CV)

Sources & evidence

ORD record
ord-744f097f0be748be96735efb2daa2075
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Linked notes

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