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Hydrochloric Acid → 4-((S)-2-methylbutoxycarbonyl)phenyl 4-benzyloxybenzoate

HRID 483949
Notes
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Reaction equation

HRID 483949 reaction equation
[CH2:1]([O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.O[C:23]1[CH:36]=[CH:35][C:26]([C:27]([O:29][CH2:30][C@@H:31]([CH3:34])[CH2:32][CH3:33])=[O:28])=[CH:25][CH:24]=1.Cl>C(Cl)(Cl)(Cl)Cl.C1(C)C=CC=CC=1.C(OCC)(=O)C.N1C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:13]([O:15][C:23]2[CH:36]=[CH:35][C:26]([C:27]([O:29][CH2:30][C@@H:31]([CH3:34])[CH2:32][CH3:33])=[O:28])=[CH:25][CH:24]=2)=[O:14])=[CH:16][CH:17]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 24386Thionyl ChlorideHCID 738804-(Benzyloxy)benzoic acidHCID 13530950Benzoic acid, 4-hydroxy-, (2S)-2-methylbutyl ester

Product 1

HCID 537644254-((S)-2-methylbutoxycarbonyl)phenyl 4-benzyloxybenzoateYield 60.7%

Reagents, catalysts & solvents 4

HCID 1049
Pyridine
Solvent
HCID 1140TolueneSolvent
HCID 5943Carbon TetrachlorideSolvent
HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

6.54 9 of p-benzyloxybenzoic acid was heated under reflux together with 12.5 g of thionyl chloride in 40 ml of carbon. tetrachloride for 3 hours. Then the unreacted thionyl chloride and carbon tetrachloride were distilled off to obtain a yellow oily residue. A solution obtained by dissolving 1.64 g of (S)-2-methylbutyl alcohol in 40.0 ml of toluene was added to the oily residue and the resulting mixture was heated under reflux for 3 hours. After completion of the reaction, 30.μ ml of ethyl acetate and 100 ml of 5 wt% hydrochloric acid were added to the reaction mixture to extract the reaction product with the ethyl acetate. Further, the ethyl acetate phase was washed with 100 ml of a 5 wt% aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of common salt and then dried over anhydrous sodium sulfate. The ethyl acetate was distilled off and the residue was subjected to silica gel column chromatography with a mixture of n-hexane and ethyl acetate (mixing ratio: 10/1 by volume) as an eluent. Thus 4.49 g of an colorless oily substance was obtained. Then the oily substance was dissolved in 15 ml of ethanol and heated under reflux in the presence of 6.75 g of cyclohexene and 0.45 g of palladium black for 1 hour. Then the palladium black was removed by filtering the reaction mixture and the ethanol and cyclohexene were distilled off. The colorless oily substance thus obtained was dissolved in 80.0 ml of toluene, washed with 20.0 ml of water and dried over anhydrous sodium sulfate. The toluene was distilled off to thereby obtain 2.99 g of (S)-2-methylbutyl 4-hydroxybenzoate (yield: 93%). Next, 0.80 g of p-benzyloxybenzoic acid was heated under reflux together with 4.17 g of thionyl chloride in 15 ml of carbon tetrachloride for 3 hours. Then the unreacted thionyl chloride and carbon tetrachloride were distilled off to obtain a yellow oily substance. A solution prepared by dissolving 0.73 g of the above-prepared (S)-2-methylbutyl 4-hydroxybenzoate in 7.00 ml of toluene was added to the oily substance. Further, 3.50 g of pyridine was added and the resulting mixture was stirred at 80° C. for 3 hours. After completion of the reaction, 30.0 ml of ethyl acetate and 50.0 ml of 5 wt% hydrochloric acid were added to extract the reaction product with the ethyl acetate. The ethyl acetate phase was washed with 50.0 ml of a 5 wt% aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of common salt and dried over anhydrous sodium sulfate. The ethyl acetate was distilled off and the residue was recrystallized from methanol to obtain 0.89 g of 4-((S)-2-methylbutoxycarbonyl)phenyl 4-benzyloxybenzoate. Then this product was dissolved in 10.0 ml of ethanol and heated under reflux in the presence of 1.01 g of cyclohexene and 0.18 g of palladium black for 1 hour. The palladium black was removed by filtering the reaction mixture and the ethanol and cyclohexene were distilled off. Thus 0.69 g of 4-((S)-2-methylbutoxycarbonyl)phenyl 4-hydroxybenzoate was obtained.

Workup

  1. distillationThen the unreacted thionyl chloride and carbon tetrachloride were distilled off
  2. customto obtain a yellow oily substance
  3. customA solution prepared
  4. additionwas added to the oily substance
  5. additionwere added
  6. extractionto extract the reaction product with the ethyl acetate
  7. washThe ethyl acetate phase was washed with 50.0 ml of a 5 wt% aqueous solution of sodium hydrogencarbonate
  8. dry with materiala saturated aqueous solution of common salt and dried over anhydrous sodium sulfate
  9. distillationThe ethyl acetate was distilled off
  10. customthe residue was recrystallized from methanol

Sources & evidence

ORD record
ord-0e5e8c3972db4b9d935b55f1b692a7a8
Source dataset
uspto-grants-1993_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05229032

Reaction notes

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