Hydrochloric Acid → HCID 18701603, compound

HRID 2288900Notes

Reaction equation

HRID 2288900 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([S:9][CH3:10])=[CH:5][CH:4]=1.Cl.[C:12]1([C:18]([CH:20](C2C=CC=CC=2)[OH:21])=[O:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[SiH3]C1C=CC=CC=1C([CH:37](C1C=CC=CC=1)[OH:38])=O.C(O)(C(F)(F)[F:48])=O.C([O-])(O)=O.[Na+]>C1COCC1.C(O)(C(F)(F)F)=O.O.C(OCC)C>[CH3:10][S:9][C:6]1[CH:7]=[CH:8][C:3]([C:20]([CH:18]([C:12]2[CH:17]=[CH:16][C:15]([O:38][CH3:37])=[C:14]([F:48])[CH:13]=2)[OH:19])=[O:21])=[CH:4][CH:5]=1

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 8400BenzoinHCID 660374-BromothioanisoleHCID 516892Sodium BicarbonateHCID 5462224MagnesiumHCID 131721876HCID 131721876, compound

Product 1

HCID 18701603HCID 18701603, compoundYield 32%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 22392675Trifluoroacetic acid waterSolvent

Procedure

Magnesium (1.34 g, 55 mmol) was suspended in THF (300 mL) and a solution of 4-bromothioanisole (10.16 g, 50 mmol) in THF (50 mL) was added dropwise over 0.5 hour maintaining the temperature at less than 30° C. The reaction was stirred an additional 0.5 hour once the addition was complete. 3-Fluoro-p-anisaldehyde silyl cyanohydrin (Example 34, Step 1) (12.7 g, 50 mmol) and diethyl ether (50 mL) were added dropwise to the solution of Grignard at such a rate that the reaction temperature did not rise above 30° C. Upon complete addition, the reaction was stirred an additional 15 minutes at which time 1N HCl (400 mL) was added and the reaction stirred until all solids were dissolved. The organics were washed with NaHCO3 (saturated) (400 mL) and brine (400 mL), dried over Na2SO4 and concentrated to yield a mixture of benzoin and silyl benzoin. The crude product was dissolved in TFA/H2O (9:1) (75 mL) and stirred for 15 minutes. The TFA solution was poured into saturated NaHCO3 (aq.). The benzoin was extracted with ethyl acetate (350 mL) and washed with NaHCO3 (saturated) (300 mL) and brine (300 mL). The crude benzoin was crystallized from ethyl acetate and hexane to yield crystals of 4-methylthio-3'-fluoro-4'-methoxybenzoin (4.9 g, 32%): 1H NMR (CDCl3) 300 MHz δ 2.45 (s, 3H), 3.81 (s, 3H), 5.8 (s, 1H), 6.86 (m, 1H), 7.01 (m, 2H), 7.17 (d, J=8.7 Hz, 2H), 7.79 (d, J=8.7 Hz, 2H); 19F NMR (CDCl3) 282 MHz δ -134.0 (multiplet).

Workup

  1. temperaturemaintaining the temperature at less than 30° C
  2. customdid not rise above 30° C
  3. additionUpon complete addition
  4. additionwas added
  5. stirringthe reaction stirred until all solids
  6. dissolutionwere dissolved
  7. washThe organics were washed with NaHCO3 (saturated) (400 mL) and brine (400 mL)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customto yield
  11. stirringstirred for 15 minutes
  12. extractionThe benzoin was extracted with ethyl acetate (350 mL)
  13. washwashed with NaHCO3 (saturated) (300 mL) and brine (300 mL)
  14. customThe crude benzoin was crystallized from ethyl acetate and hexane

Sources & evidence

ORD record
ord-e4f8c9676e1449c2bf22a10d5188cebf
Source dataset
uspto-grants-2000_07
Patent number
US06090834

Reaction notes

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