Triphenylphosphine → (S)-4,5-difluoro-2-(pent-4-en-2-yloxy)benzaldehyde

HRID 921129

Reaction equation

HRID 921129 reaction equation
[F:1][C:2]1[C:9]([F:10])=[CH:8][C:5]([CH:6]=[O:7])=[C:4]([OH:11])[CH:3]=1.[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[C:9]([F:10])=[CH:8][C:5]([CH:6]=[O:7])=[C:4]([O:11][C@H:15]([CH2:14][CH:13]=[CH2:12])[CH3:16])[CH:3]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 6999724(2R)-pent-4-en-2-olHCID 154345534,5-Difluoro-2-hydroxybenzaldehyde

Product 1

HCID 118307018(S)-4,5-difluoro-2-(pent-4-en-2-yloxy)benzaldehydeYield 9.05%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4,5-difluoro-2-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). DIAD (1.599 ml, 8.22 mmol) was added dropwise (exotherm) and the mixture was stirred at rt. After 1.5 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 yellow oil was purified by flash chromatography (Biotage; 0%-100% EtOAc/hexane; 20 CV) to give (S)-4,5-difluoro-2-(pent-4-en-2-yloxy)benzaldehyde (0.1295 g, 0.572 mmol, 9.05% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 10.36 (d, J=3.2 Hz, 1H), 7.76-7.55 (m, 1H), 6.83 (dd, J=11.9, 6.0 Hz, 1H), 6.04-5.67 (m, 1H), 5.23-5.06 (m, 2H), 4.48 (sxt, J=6.0 Hz, 1H), 2.71-2.35 (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 yellow oil was purified by flash chromatography (Biotage; 0%-100% EtOAc/hexane; 20 CV)

Sources & evidence

ORD record
ord-4b29f591b603425e81dc27f63be7a1ef
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Linked notes

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