Citric Acid → 3-[3-(5-Chloro-2-methoxyphenylsulfonyloxy)-5-methylphenoxy]propionaldehyde

HRID 442940Notes

Reaction equation

HRID 442940 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:24][CH3:25])=[C:6]([S:8]([O:11][C:12]2[CH:13]=[C:14]([CH:20]=[C:21]([CH3:23])[CH:22]=2)[O:15][CH2:16][CH2:17][CH2:18][OH:19])(=[O:10])=[O:9])[CH:7]=1.C(N(CC)C(C)C)(C)C.CS(C)=O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:24][CH3:25])=[C:6]([S:8]([O:11][C:12]2[CH:13]=[C:14]([CH:20]=[C:21]([CH3:23])[CH:22]=2)[O:15][CH2:16][CH2:17][CH:18]=[O:19])(=[O:9])=[O:10])[CH:7]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 679Dimethyl SulfoxideHCID 81531DiisopropylethylamineHCID 227224523-[3-(5-Chloro-2-methoxyphenylsulfonyloxy)-5-methylphenoxy]propanol

Product 1

HCID 539733043-[3-(5-Chloro-2-methoxyphenylsulfonyloxy)-5-methylphenoxy]propionaldehydeYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) solution of 3-[3-(5-chloro-2-methoxyphenylsulfonyloxy)-5-methylphenoxy]propanol (3.32 g, 8.58 mmol), N,N-diisopropylethylamine (3.14 mL, 18.0 mmol), and anhydrous dimethyl sulfoxide (1.83 mL, 25.7 mmol) in anhydrous dichloromethane (20 mL) under nitrogen was added sulfur trioxide pyridine complex (2.73 g, 17.1 mmol) portionwise over 23 minutes. The solution was stirred at 0° C. for 1 hour then quenched with 5% w/v aqueous citric acid (200 mL, 48 mmol). The mixture was extracted with diethyl ether (250 mL). The aqueous layer was extracted with diethyl ether (2×100 mL), and the combined organic extracts were washed with pH 7 buffer (100 mL) and brine (100 mL). The organic layer was dried over Na2SO4, filtered, and evaporated. Crude product was purified by flash column chromatography through silica gel (50% to 70% diethyl ether in hexane) to give the title compound as a gold oil (2.34 g, 71%). 1H-NMR (300 MHz, CDCl3) δ 9.81 (t, 1 H, J=1.5 Hz), 7.79 (d, 1 H, J=2.7 Hz), 7.54 (dd, 1 H, J=2.7, 8.9 Hz), 7.01 (d, 1 H, J=8.9 Hz), 6.54-6.60 (m, 1 H), 6.52-6.53 (m, 1 H), 6.43-6.44 (m, 1 H), 4.19 (t, 2 H, J=6.1 Hz), 3.99 (s, 3 H), 2.85 (td, 2 H, J=1.5, 6.1 Hz), 2.25 (d, 3 H, J=0.5 Hz). Mass spectrum (MALDI-TOF, α-cyano4- hydroxycinnamic acid matrix) calcd. for C17H17ClO6S: 407.0 (M+Na). Found: 407.0.

Workup

  1. additionwas added sulfur trioxide pyridine complex (2.73 g, 17.1 mmol) portionwise over 23 minutes
  2. extractionThe mixture was extracted with diethyl ether (250 mL)
  3. extractionThe aqueous layer was extracted with diethyl ether (2×100 mL)
  4. washthe combined organic extracts were washed with pH 7 buffer (100 mL) and brine (100 mL)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customCrude product was purified by flash column chromatography through silica gel (50% to 70% diethyl ether in hexane)

Sources & evidence

ORD record
ord-6b84561ef91b437c8a50364938af4d20
Source dataset
uspto-grants-1999_04
Patent number
US05891909

Reaction notes

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