Diisopropylamine → HCID 23570948, compound

HRID 1823925Notes

Reaction equation

HRID 1823925 reaction equation
C(NC(C)C)(C)C.[CH3:8][O:9][C:10](=[O:20])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=1.Br[CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24]>O1CCCC1>[CH3:8][O:9][C:10](=[O:20])[CH:11]([C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=1)[CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24]

Participants

5

Reactant 3

HCID 7912DiisopropylamineHCID 79177tert-Butyl bromoacetateHCID 1268257Methyl 2-(3,4-dichlorophenyl)acetate

Product 1

HCID 23570948HCID 23570948, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

2.5M nButyllithium in hexanes (37.5 ml, 0.094 mol) was added, in a dropwise fashion, to a solution of diisopropylamine (14.45 ml, 0.103 mol) in tetrahydrofuran (300 ml) at 0° C. The solution was stirred at 0° C. for 20 minutes. The mixture was then cooled to −70° C. and a solution of (3,4-dichloro-phenyl)-acetic acid methyl ester (20.54 g, 0.094 mol) in tetrahydrofuran (50 ml) was added dropwise via cannula. The reaction mixture was stirred at −70° C. for 30 minutes. After this time, tert-butyl bromoacetate (45.42 ml, 0.281 mol) was added in a dropwise fashion. The cooling bath was removed and the reaction mixture was allowed to warm up to room temperature. The reaction mixture was quenched with a saturated solution of NH4Cl (100 ml). THF was partially removed in vacuo and the mixture was extracted with EtOAc (3×200 ml). The combined organic extrats were washed with brine, dried (MgSO4) and concentrated in vacuo. The crude mixture was purified by silica gel column chromatography using as eluent petrol: ether (9:1) to give the title compound in 92% yield.). 1H NMR (400 MHz, DMSO-d6) δ 1.34 (9H, s), 2.65 (1H, dd), 2.98 (1H, dd), 3.60 (3H, s), 4.08 (1H, m), 7.31 (1H, m), 7.58–7.62 (2H, m); MS (ES+): m/e=333.2 (5%); MS (ES−): m/e=331.2 (100%), 333.2 (65%), 335.2 (10%).

Workup

  1. temperatureThe mixture was then cooled to −70° C.
  2. stirringThe reaction mixture was stirred at −70° C. for 30 minutes
  3. customThe cooling bath was removed
  4. temperatureto warm up to room temperature
  5. customThe reaction mixture was quenched with a saturated solution of NH4Cl (100 ml)
  6. customTHF was partially removed in vacuo
  7. extractionthe mixture was extracted with EtOAc (3×200 ml)
  8. washThe combined organic extrats were washed with brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. customThe crude mixture was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-e9ff79ec3c2a414594a38db6af480c38
Source dataset
uspto-grants-2006_05
Patent number
US07041687B2

Reaction notes

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