Triphenylphosphine → 3-[(2,3-Dihydro-1H-inden-2-yl)oxy]-4-methoxybenzaldehyde

HRID 2301405Notes

Reaction equation

HRID 2301405 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH:5]=[O:6].[CH2:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH:13]1O.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.C(OCC)C>[CH2:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH:13]1[O:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH:5]=[O:6]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 12127IsovanillinHCID 779362-IndanolHCID 5363146Diisopropyl azodicarboxylate

Product 1

HCID 157288423-[(2,3-Dihydro-1H-inden-2-yl)oxy]-4-methoxybenzaldehydeYield 20.7%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-hydroxy-4-methoxy-benzaldehyde (15.2 g, 100 mmol, 1 eq), 2-indanol (12.1 g, 90 mmol, 0.9 eq), and triphenylphosphine (26.2 g, 100 mmol, 1 eq) in dry THF (300 mL) was treated dropwise with diisopropylazodicarboxylate (19.6 mL, 100 mmol, 1 eq). The reaction mixture was stirred at reflux for 16 hours, then cooled and diluted with diethyl ether (500 mL). The solution was washed with water (2×150 mL), 1 M NaOH (4×125 mL), and saturated NaCl (sodium chloride) (2×100 mL), dried with CH2Cl2, then concentrated to provide a syrup, which solidified upon standing. The solid was suspended in diethyl ether (350 mL) and stirred overnight to break up all chunks. The solid was collected by vacuum filtration and recrystallized from ethanol/water (21.4 g). The ethereal filtrate was concentrated and purified by flash chromatography (silica gel, 7.5×36 cm Biotage KP-Sil column, eluted with 25% ethyl acetate in heptane) to yield an additional 5 g of product. 1H NMR (300 MHz, CDCl3) δ 9.86 (s, 1H), 7.49-7.44 (m, 2H), 7.25-7.16 (m, 4H), 6.97 (d, J=8.7 Hz, 1H), 5.29-5.22 (m, 1H), 3.89 (s, 1H), 3.45 (dd, J=16.7, 6.6 Hz, 2H), 3.24 (dd, J=16.7, 3.6 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ 190.9, 155.5, 147.9, 140.4, 130.0, 126.9, 126.8, 124.7, 112.1, 111.0, 78.9, 56.1, 39.7.

Workup

  1. temperatureat reflux for 16 hours
  2. temperaturecooled
  3. washThe solution was washed with water (2×150 mL), 1 M NaOH (4×125 mL), and saturated NaCl (sodium chloride) (2×100 mL)
  4. dry with materialdried with CH2Cl2
  5. concentrationconcentrated
  6. customto provide a syrup, which
  7. stirringstirred overnight
  8. filtrationThe solid was collected by vacuum filtration
  9. customrecrystallized from ethanol/water (21.4 g)
  10. concentrationThe ethereal filtrate was concentrated
  11. custompurified by flash chromatography (silica gel, 7.5×36 cm Biotage KP-Sil column, eluted with 25% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-aa8b070bbaa94c54b8a84d59e195c593
Source dataset
uspto-grants-2002_12
Patent number
US06500856B2

Reaction notes

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