Acetyl chloride → methyl 2-(6-acetyl-5-methoxy-2,3-dihydro-1H-inden-1-yl)butanoate

HRID 900530Notes

Reaction equation

HRID 900530 reaction equation
[Al+3].[Cl-].[Cl-].[Cl-].[C:5](Cl)(=[O:7])[CH3:6].[CH3:9][O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[CH:16]([CH:20]([CH2:25][CH3:26])[C:21]([O:23][CH3:24])=[O:22])[CH2:15][CH2:14]2>C(Cl)Cl>[C:5]([C:19]1[CH:18]=[C:17]2[C:13]([CH2:14][CH2:15][CH:16]2[CH:20]([CH2:25][CH3:26])[C:21]([O:23][CH3:24])=[O:22])=[CH:12][C:11]=1[O:10][CH3:9])(=[O:7])[CH3:6]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 23529443methyl 5-methoxy-2,3-dihydro-1H-indene-1-yl-butanoate

Product 1

HCID 21942762methyl 2-(6-acetyl-5-methoxy-2,3-dihydro-1H-inden-1-yl)butanoateYield 68.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of AlCl3 (103 mg, 0.78 mmol) in methylene chloride (2.5 mL) at 0° C., was added acetyl chloride (0.044 mL, 0.63 mmol), followed by the addition of a solution of methyl 5-methoxy-2,3-dihydro-1H-indene-1-yl-butanoate (130 mg, 0.52 mmol) in methylene chloride (2.7 mL) dropwise. The mixture was stirred at 0° C. for 15 minutes. The ice bath was removed and the mixture stirred at rt for 16 hours. The mixture was poured over ice and 4 drops of conc. HCl were added. This mixture was extracted with methylene chloride twice. The combined organic layers were washed with water, 0.05 N NaOH and water. The organic layer was dried, concentrated, and purified by chromatography with 10% EtOAc:hexane to give desired product (103 mg, 68%). Rf=0.28 (4:1 hexane:EtOAc); GC-MS (+Cl): m/z=291 (M+); 1H NMR (DMSO-d6): δ 0.840 (m, 3H), 1.536 (m, 2H), 1.876 (m, 1H), 2.108 (m, 1H), 2.505 (s, 3H), 2.521 (m, 1H), 2.760-2.889 (m, 2H), 3.236 (m, 1H), 3.511 and 3.589 (s, 3H), 3.836 (s, 3H), 7.012 and 7.253 (s, 1H), 7.440 (s, 1H).

Workup

  1. customThe ice bath was removed
  2. stirringthe mixture stirred at rt for 16 hours
  3. additionThe mixture was poured over ice and 4 drops of conc. HCl
  4. additionwere added
  5. extractionThis mixture was extracted with methylene chloride twice
  6. washThe combined organic layers were washed with water, 0.05 N NaOH and water
  7. customThe organic layer was dried
  8. concentrationconcentrated
  9. custompurified by chromatography with 10% EtOAc

Sources & evidence

ORD record
ord-69a19f33a2f24045a9cd4c0e65f2b4e8
Source dataset
uspto-grants-2008_04
Patent number
US07358386B2

Reaction notes

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