Pyridine → HCID 59199372, compound

HRID 2089551Notes

Reaction equation

HRID 2089551 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[C:8]([CH3:13])([CH3:12])[CH:7]2[OH:14].N1C=CC=CC=1.[C:21](OC(=O)C)(=[O:23])[CH3:22].[BH4-].[Na+]>ClCCl.O.C(O)C.[NH4+].[Cl-]>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[CH:9]([OH:11])[C:8]([CH3:12])([CH3:13])[CH:7]2[O:14][C:21](=[O:23])[CH3:22]

Participants

9

Reactant 4

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 4311764Sodium borohydride2×HCID 59199367HCID 59199367, compound

Product 1

HCID 59199372HCID 59199372, compound

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of 7-chloro-3-hydroxy-2,2-dimethyl-indan-1-one, which can be prepared as described in Example 58, (287 mg, 1.36 mmol) in dichloromethane (15 mL) is added pyridine (1.1 mL, 13.6 mmol), and acetic anhydride (0.26 mL, 2.72 mmol). The reaction is permitted to stir for 1 hour and is then diluted with water and extracted twice with dichloromethane. The combined organic extracts are washed successively with 4N aqueous HCl and saturated aqueous NaHCO3, dried over Na2SO4, filtered and concentrated. The resulting residue is then diluted with ethanol (10.0 mL) and cooled to −10° C. The solution is then charged with a solution of NaBH4 (100 mg, 2.63 mmol) in ethanol (6 mL). The reaction is permitted to warm to room temperature over 1 hour, at which time additional NaBH4 (50 mg, 1.31 mmol) is added. The reaction is permitted to stir for another 1.5 hours and then diluted with saturated aqueous NH4Cl. The reaction mixture is concentrated to remove the organic volatiles and then extracted three times with ethyl acetate. The organic extracts are combined, dried over Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:2) to furnish acetic acid 4-chloro-3-hydroxy-2,2-dimethyl-indan-1-yl ester; MS: (ESI) m/z 237.17 (M−OH)+

Workup

  1. extractionextracted twice with dichloromethane
  2. washThe combined organic extracts are washed successively with 4N aqueous HCl and saturated aqueous NaHCO3
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additionThe resulting residue is then diluted with ethanol (10.0 mL)
  7. additionis added
  8. stirringto stir for another 1.5 hours
  9. concentrationThe reaction mixture is concentrated
  10. customto remove the organic volatiles
  11. extractionextracted three times with ethyl acetate
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:2)

Sources & evidence

ORD record
ord-72c3e4b755fc4baebb4efd064530f14d
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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