Hydrochloric Acid → Methyl 2-(6-methoxy-1H-inden-3-yl)butanoate

HRID 1454026Notes

Reaction equation

HRID 1454026 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=O)[CH2:7][CH2:6]2.Br[CH:14]([CH2:19][CH3:20])[C:15]([O:17][CH3:18])=[O:16].Cl>C1COCC1.[Zn]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9]([C:8]([CH:14]([CH2:19][CH3:20])[C:15]([O:17][CH3:18])=[O:16])=[CH:7][CH2:6]2)=[CH:10][CH:11]=1

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 787875-Methoxyindan-1-oneHCID 95577Butanoic acid, 2-bromo-, methyl ester

Product 1

HCID 11402344Methyl 2-(6-methoxy-1H-inden-3-yl)butanoateYield 104.4%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

An oven dried 5-L four-necked round-bottomed flask was fitted with a thermometer, a condenser, an addition funnel, and a mechanical stirrer. Under an argon atmosphere, a suspension of 5-methoxy-1-indanone (80.0 g, 494 mmol), Zn powder (Lancaster, 56.2 g, 865 mmol) in THF (2 L, anhydrous) was stirred at 60° C. (internal temperature), while a solution of methyl bromobutyrate (134.1 g, 741 mmol) in THF (400 mL, anhydrous) was added slowly using an addition funnel. After completion of the addition, the reaction mixture was stirred at 60° C. (internal temperature) for 1 h. The reaction was followed by TLC analysis of aliquots following 1 N aqueous HCl workup. After the reaction was completed, it was cooled in an ice-water bath followed by slow addition HCl (3 L, 1 N aqueous solution). The internal temperature was kept below 20° C. The mixture was then extracted with EtOAc (1 L). The organic layer was washed with water until pH 6.0-7.0, then with brine, dried over Na2SO4, and then filtered. The product (127 g, >99%), a yellow oil, was obtained after solvent removal and drying under vacuum. 1H NMR (300 MHz), (DMSO-d6) δ 7.28 (d, 1H), 7.05 (d, 1H), 6.82 (dd, 1H), 6.22 (s, 1H), 3.72 (s, 3H), 3.60 (m, 1H), 3.58 (s, 3H), 3.28 (s, 2H), 1.95 (m, 1H), 1.80 (m, 1H), 0.88 (t, 3H).

Workup

  1. dry with materialAn oven dried 5-L four-necked round-bottomed flask
  2. customwas fitted with a thermometer, a condenser, an addition funnel, and a mechanical stirrer
  3. additionAfter completion of the addition
  4. stirringthe reaction mixture was stirred at 60° C. (internal temperature) for 1 h
  5. temperatureit was cooled in an ice-water bath
  6. customwas kept below 20° C
  7. extractionThe mixture was then extracted with EtOAc (1 L)
  8. washThe organic layer was washed with water until pH 6.0-7.0
  9. dry with materialwith brine, dried over Na2SO4
  10. filtrationfiltered

Sources & evidence

ORD record
ord-d04d8ecc13ce4fe4a841868e322b977c
Source dataset
uspto-grants-2009_01
Patent number
US07476742B2

Reaction notes

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