Sodium hydride → HCID 59300428, compound

HRID 603514Notes

Reaction equation

HRID 603514 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@H:7]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:6][CH2:5]2.[H-].[Na+].[CH3:19][N:20]([CH3:24])[C:21](Cl)=[S:22].[NH4+].[Cl-]>CN(C=O)C>[CH3:19][N:20]([CH3:24])[C:21]([O:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C@H:7]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:6][CH2:5]2)=[S:22]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 27871Dimethylthiocarbamoyl chlorideHCID 16110404ethyl 2-[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetate

Product 1

HCID 59300428HCID 59300428, compoundYield 68.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of ethyl [(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetate (620 mg, 2.81 mmol) (Example 6) in DMF (20 mL) was added NaH (124 mg, 3.10 mmol, 60% dispersion in mineral oil). Once the gaseous evolution had subsided (˜10 min), dimethylthiocarbamoyl chloride (382 mg, 3.10 mmol) was added. The solution was stirred at rt for 16 h, then at 60° C. for an additional 8 h. The reaction mixture was cooled to rt, a saturated solution of NH4Cl added, and the aqueous phase was extracted with ether. The combined organic phases were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (8:1 hexanes/EtOAc) to give the title compound as a yellowish oil (590 mg, 68%). 1H NMR (400 MHz, CDCl3) 7.16 (d, 1H), 6.90 (s, 1H), 6.84 (dd, 1H), 4.18 (q, 2H), 3.63-3.51 (m, 1H), 3.46 (s, 3H), 3.30 (s, 3H), 2.98-2.84 (m, 2H), 2.78 (dd, 1H), 2.49-2.37 (m, 2H), 1.85-1.75 (m, 1H), 1.29 (t, 3H); LC-MS: RT=3.18 min, (M+H)+ 308.1.

Workup

  1. additionwas added
  2. waitat 60° C. for an additional 8 h
  3. temperatureThe reaction mixture was cooled to rt
  4. extractionthe aqueous phase was extracted with ether
  5. dry with materialThe combined organic phases were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel flash chromatography (8:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-55819458668f482e892856c5520870b3
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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