Hydrochloric Acid → HCID 87384391, compound

HRID 1401259Notes

Reaction equation

HRID 1401259 reaction equation
[Li][CH2:2][CH2:3][CH2:4]C.C[Si](C)(C)N[Si](C)(C)C.[C:15]([O:18][CH2:19][C@H:20]1[C@H:24]([C:25]2[C:30]([O:31][CH3:32])=[CH:29][C:28]([O:33][CH3:34])=[C:27]([C:35](=[O:37])[CH3:36])[C:26]=2[O:38]C(=O)C2C=CC=C(Cl)C=2)[CH2:23][CH2:22][N:21]1[CH3:48])(=[O:17])[CH3:16].[ClH:49].C(=O)(O)[O-].[Na+].[CH2:55]1[CH2:59][O:58][CH2:57][CH2:56]1>>[Cl:49][C:3]1[CH:4]=[C:55]([C:59](=[O:58])[CH2:36][C:35]([C:27]2[C:26]([OH:38])=[C:25]([CH:24]3[CH2:23][CH2:22][N:21]([CH3:48])[CH:20]3[CH2:19][O:18][C:15](=[O:17])[CH3:16])[C:30]([O:31][CH3:32])=[CH:29][C:28]=2[O:33][CH3:34])=[O:37])[CH:56]=[CH:57][CH:2]=1

Participants

7

Reactant 6

HCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran2×HCID 13838HexamethyldisilazaneHCID 516892Sodium BicarbonateHCID 131732149HCID 131732149, compoundHCID 178418339Butyllithium

Product 1

HCID 87384391HCID 87384391, compound

Conditions

Temperature
0 °C

Procedure

To a solution of n-BuLi (15% solution in hexane, 8.2 mL, 19.25 mmol) in THF (30 mL), maintained at 0° C. under nitrogen atmosphere, hexamethyldisilazane (4.06 mL, 19.9 mmol) was added drop wise and stirred for 15 minutes. To this, a solution of compound of example 31 (3.8 g, 7.75 mmol) in THF (30 mL) was added drop wise, maintaining the temperature at 0° C. After the addition, the reaction was allowed to warm to room temperature and stirred for 2.5 hours. The reaction mixture was acidified with dilute HCl, and basified with 10% sodium bicarbonate to pH 8-9. The aqueous layer was extracted with chloroform (3×75 mL). The organic layer was washed with water (50 mL), brine (50 mL) and dried over anhydrous Na2SO4. The organic layer was concentrated under reduced pressure and dried under vacuum to obtain acetic acid 3-{3-[3-(3-chloro-phenyl)-3-oxo-propionyl]-2-hydroxy-4,6-dimethoxy-phenyl}-1-methyl-pyrrolidin-2-ylmethyl ester as an oil (2.7 g), which was dissolved in conc. HCl (60 mL) and stirred for 3 hours to effect cyclisation. At the end of 3 hours, the reaction mixture was basified with solid NaHCO3 to pH 8-9. The aqueous layer was extracted with chloroform (50×3 mL) and washed with water (25 mL) and brine (25 mL). The organic layer was dried over anhydrous Na2SO4, concentrated under reduced pressure and dried over vacuum. The residue was purified by column chromatography with 3% methanol in chloroform and 0.01% ammonia as eluent to afford the title compound.

Workup

  1. additionAfter the addition
  2. temperatureto warm to room temperature
  3. stirringstirred for 2.5 hours
  4. extractionThe aqueous layer was extracted with chloroform (3×75 mL)
  5. washThe organic layer was washed with water (50 mL), brine (50 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationThe organic layer was concentrated under reduced pressure
  8. customdried under vacuum

Sources & evidence

ORD record
ord-be6d4a28e31e42498b52b284d45929bd
Source dataset
uspto-grants-2014_12
Patent number
US08906953B2

Reaction notes

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