Sodium Chloride → 2-[2-(3,4-dihydro-1H-isoquinolin-2-yl)-2-oxo-ethyl]-4-methyl-pentanoic acid

HRID 719600Notes

Reaction equation

HRID 719600 reaction equation
O.[OH-].[Li+].C[O:5][C:6](=[O:25])[CH:7]([CH2:12][C:13]([N:15]1[CH2:24][CH2:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16]1)=[O:14])[CH2:8][CH:9]([CH3:11])[CH3:10].[Cl-].[Na+]>O.O1CCCC1.CO>[CH2:16]1[C:17]2[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:23][CH2:24][N:15]1[C:13](=[O:14])[CH2:12][CH:7]([CH2:8][CH:9]([CH3:10])[CH3:11])[C:6]([OH:25])=[O:5]

Participants

6

Reactant 3

HCID 5234Sodium ChlorideHCID 168937Lithium hydroxide, monohydrateHCID 69593328HCID 69593328, compound

Product 1

HCID 218998372-[2-(3,4-dihydro-1H-isoquinolin-2-yl)-2-oxo-ethyl]-4-methyl-pentanoic acidYield 12%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A solution of lithium hydroxide monohydrate (0.01452 g, 0.3461 mmol) in water (1.5 ml) was added drop-wise over 1 minute to a solution of 2-[2-(3,4-dihydro-1H-isoquinolin-2-yl)-2-oxo-ethyl]-4-methyl-pentanoic acid methyl ester (0.035 g, 0.1154 mmol) in tetrahydrofuran:methanol 2:1 (9 ml) at 0° C. The mixture was stirred at ambient temperature for 16 hours then poured into saturated aqueous sodium chloride solution (10 ml). The aqueous layer was extracted with diethyl ether (2×10 ml) which was discarded. The aqueous layer was acidified with 1M hydrochloric acid to pH (1˜2), then the product was extracted into dichloromethane (3×10 ml). The combined dichloromethane layers were washed with water (2×10 ml), saturated aqueous sodium chloride solution (2×10 ml) then dried (Na2SO4) and the solvents removed in vacuo to leave 2-[2-(3,4-dihydro-1H-isoquinolin-2-yl)-2-oxo-ethyl]-4-methyl-pentanoic acid as a colourless oil (4.0 mg, 12%). TLC (main spot, Rf=0.2, methanol:dichloromethane 1:10), analytical HPLC Rt=13.297 min. HPLC-MS (290.2 [M+1]+, 312.2 [M+Na]+, 601.3 [2M+Na]+).

Workup

  1. extractionThe aqueous layer was extracted with diethyl ether (2×10 ml) which
  2. extractionthe product was extracted into dichloromethane (3×10 ml)
  3. washThe combined dichloromethane layers were washed with water (2×10 ml), saturated aqueous sodium chloride solution (2×10 ml)
  4. dry with materialthen dried (Na2SO4)
  5. customthe solvents removed in vacuo

Sources & evidence

ORD record
ord-44c37159df3b4b088e8b405efe1422ee
Source dataset
uspto-grants-2006_11
Patent number
US07132449B2

Reaction notes

Loading…