Hydrochloric Acid → 3H-spiro[2-benzofuran-1,4'-piperidine]

HRID 2256062Notes

Reaction equation

HRID 2256062 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].O=[C:8]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:10]2([CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[O:9]1.B(F)(F)F.CCOCC.Cl>O1CCCC1.O>[NH:13]1[CH2:14][CH2:15][C:10]2([C:16]3[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:8][O:9]2)[CH2:11][CH2:12]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8000Boron trifluoride etherateHCID 98342553H-spiro(isobenzofuran-1,4'-piperidin)-3-oneHCID 21226445Aluminium lithium hydride

Product 1

HCID 104424983H-spiro[2-benzofuran-1,4'-piperidine]Yield 79.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of lithium aluminum hydride (7.5 mL 1M in ether) diluted with 35 mL of tetrahydrofuran was cooled to 0° C. and added to a suspension of 3-oxospiro[isobenzofuran-1(3H),4'-piperidine] (0.38 g) in 40 mL of anhydrous tetrahydrofuran containing boron trifluoride etherate (6.9 mL). The reaction mixture was allowed to warm to room temperature and then refluxed for 3 hours. At the end of this period, the reaction mixture was cooled in ice and treated with 5% HCl (8 mL) followed by water (8 mL). After concentrating under reduced pressure, the reaction mixture was treated with concentrated HCl (8 mL) and heated to reflux, cooled to room temperature, the pH was adjusted to 5 by adding sodium hydroxide solution and extracted with ether. The aqueous layer was made basic (pH 11) with sodium hydroxide and extracted with two portions of dichloromethane. The dichloromethane layer was dried and evaporated to afford the named product (0.28 g) which was used in the next step without further purification; MS: 190; NMR: 7-1.1.9 (m, 4), 2.9-3.1 (m, 4), 5.1 (s, 2), 7.1-7.3 (m, 4).

Workup

  1. temperatureto warm to room temperature
  2. temperaturerefluxed for 3 hours
  3. temperatureAt the end of this period, the reaction mixture was cooled in ice
  4. concentrationAfter concentrating under reduced pressure
  5. additionthe reaction mixture was treated with concentrated HCl (8 mL)
  6. temperatureheated
  7. temperatureto reflux
  8. temperaturecooled to room temperature
  9. additionby adding sodium hydroxide solution
  10. extractionextracted with ether
  11. extractionextracted with two portions of dichloromethane
  12. dry with materialThe dichloromethane layer was dried
  13. customevaporated

Sources & evidence

ORD record
ord-77acae2abc5244a2b8020bb08f2c8813
Source dataset
uspto-grants-1997_08
Patent number
US05654299

Reaction notes

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