Hydrochloric Acid → 2,2-Dimethyl-3-(3-benzyloxyphenyl)propionic Acid

HRID 902711Notes

Reaction equation

HRID 902711 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[C:13]([OH:18])(=[O:17])[CH:14]([CH3:16])[CH3:15].CN(P(N(C)C)(N(C)C)=O)C.[CH2:30]([O:37][C:38]1[CH:39]=[C:40]([CH:43]=[CH:44][CH:45]=1)[CH2:41]Cl)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.Cl>C1COCC1.O>[CH3:15][C:14]([CH3:16])([CH2:41][C:40]1[CH:43]=[CH:44][CH:45]=[C:38]([O:37][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:39]=1)[C:13]([OH:18])=[O:17]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 6590Isobutyric AcidHCID 7912DiisopropylamineHCID 12679HexamethylphosphoramideHCID 131734903-(Benzyloxy)benzyl chlorideHCID 178418339Butyllithium

Product 1

HCID 688617242,2-Dimethyl-3-(3-benzyloxyphenyl)propionic AcidYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of diisopropylamine (1.55 mL, 11.9 mmole) in 20 mL of THF was cooled to −78° and treated with n-BuLi (6.5 mL 1.6N solution in hexane, 10.4 mmole). After 10 minutes, a solution of isobutyric acid (436 mg, 4.96 mmole) in 3 mL of THF was added, followed by HMPA (1.74 mL, 10 mmole). The reaction was allowed to warm to 23°, then heated at 55° for 30 minutes. The reaction was cooled to −78° and a solution of 3-benzyloxybenzyl chloride (1.15 g, 4.96 mmole) in 6 mL of THF was added. The reaction was warmed to 23° for 30 minutes, then heated at 55° for 30 minutes. The reaction was cooled, diluted with H2O, acidified with 3N HCl, and extracted with Et2O. The extracts were washed three times with H2O, dried and the solvent removed, and gave the titled compound as a white powder, 1.2 g (85% yield). MS (ESI) 285 (MH+).

Workup

  1. temperatureto warm to 23°
  2. temperatureheated at 55° for 30 minutes
  3. temperatureThe reaction was cooled to −78°
  4. temperatureThe reaction was warmed to 23° for 30 minutes
  5. temperatureheated at 55° for 30 minutes
  6. temperatureThe reaction was cooled
  7. extractionextracted with Et2O
  8. washThe extracts were washed three times with H2O
  9. customdried
  10. customthe solvent removed

Sources & evidence

ORD record
ord-e16162a2c7a04c8a96084ab19e1f4ba6
Source dataset
uspto-grants-2008_04
Patent number
US07365085B2

Reaction notes

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