Lithium Hydroxide → 5-Bromo-2-(3-tert-butoxycarbonyl-propoxy)-4-chloro-benzoic acid

HRID 1848638Notes

Reaction equation

HRID 1848638 reaction equation
C(OC(CCC[O:11][C:12](=[O:32])[C:13]1[CH:18]=[C:17]([Br:19])[C:16]([Cl:20])=[CH:15][C:14]=1[O:21][CH2:22][CH2:23][CH2:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=O)(C)(C)C.[Li+].[OH-].OS([O-])(=O)=O.[Na+]>C1COCC1>[Br:19][C:17]1[C:16]([Cl:20])=[CH:15][C:14]([O:21][CH2:22][CH2:23][CH2:24][C:25]([O:27][C:28]([CH3:30])([CH3:29])[CH3:31])=[O:26])=[C:13]([CH:18]=1)[C:12]([OH:32])=[O:11]

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 516919Sodium BisulfateHCID 686035915-Bromo-2-(3-tert-butoxycarbonyl-propoxy)-4-chloro-benzoic acid 3-tert-butoxycarbonyl-propyl ester

Product 1

HCID 686032665-Bromo-2-(3-tert-butoxycarbonyl-propoxy)-4-chloro-benzoic acidYield 41.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 5-bromo-2-(3-tert-butoxycarbonyl-propoxy)-4-chloro-benzoic acid 3-tert-butoxycarbonyl-propyl ester (8.2 g, 15.3 mmol) and LiOH (19.1 mL, 4 N, 76.6 mmol) in THF (150 mL) was stirred at rt for 16 hrs. The mixture was acidified by saturated NaHSO4 (50 mL) and extracted with ethyl acetate. The ethyl acetate layer was dried over Na2SO4, filtered and concentrated. The residue was purified via silica gel flash chromatography (eluting with 50% ethyl acetate in hexane), followed by crystallization in hexane/ethyl acetate (10/1) to afford 5-bromo-2-(3-tert-butoxycarbonyl-propoxy)-4-chloro-benzoic acid as white crystals (2.5 g). MS [M-(iso-butene+OH)]+: 320.8; tR=2.38 min. (method 1)

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe ethyl acetate layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified via silica gel flash chromatography (eluting with 50% ethyl acetate in hexane)
  6. customfollowed by crystallization in hexane/ethyl acetate (10/1)

Sources & evidence

ORD record
ord-87387904f7ba4ffaa599f0ff304bb6ea
Source dataset
uspto-grants-2015_02
Patent number
US08952161B2

Reaction notes

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