Ammonium Chloride → HCID 58042307, compound

HRID 1619691Notes

Reaction equation

HRID 1619691 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][NH:6][C:7]1[S:8][CH:9]=[CH:10][N:11]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[C:28]([C:30]1[CH:31]=[C:32]([S:37](Cl)(=[O:39])=[O:38])[CH:33]=[CH:34][C:35]=1[F:36])#[N:29].[Cl-].[NH4+]>O1CCCC1>[C:28]([C:30]1[CH:31]=[C:32]([S:37]([N:6]([CH2:5][C:4]2[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:3]=2[O:2][CH3:1])[C:7]2[S:8][CH:9]=[CH:10][N:11]=2)(=[O:39])=[O:38])[CH:33]=[CH:34][C:35]=1[F:36])#[N:29]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 27789083-Cyano-4-fluorobenzenesulfonyl chlorideHCID 49931979N-(2,4-dimethoxybenzyl)thiazol-2-amine

Product 1

HCID 58042307HCID 58042307, compoundYield 25.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

N-(2,4-Dimethoxybenzyl)-1,3-thiazol-2-yl-amine (Preparation 91, 8.010 g, 0.032 mol) was dissolved in tetrahydrofuran (100 mL) and the solution was cooled to −78° C. Lithium hexamethyldisilazide in tetrahydrofuran (35.2 mL, 1M) was added dropwise to the reaction mixture. The cooling bath was removed and the reaction mixture was allowed to stir for 30 minutes to attain room temperature before re-cooling to −78° C. and a solution of 3-cyano-4-fluorobenzenesulfonyl chloride (7.028 g, 0.032 mol) in tetrahydrofuran (80 mL) was added dropwise to the reaction mixture. The reaction was allowed to stir 30 minutes at −78° C. before pouring it into saturated aqueous ammonium chloride (50 mL). The aqueous phase was separated and extracted with ethyl acetate (3×30 mL). The combined organic phases were washed twice with 10% aqueous citric acid solution (30 mL), water (30 mL), brine (20 mL), dried over MgSO4, filtered and evaporated. The residue was purified by column chromatography (120 g silica gel column, hexanes/ethyl acetate gradient elution 100/0 to 0/100). Product fractions were combined and evaporated. The residue was triturated with 10% tert-butyl methyl ether in hexanes and the resulting off-white solid collected by filtration and rinsed with hexanes and vacuum dried to provide the title compound (3.58 g).

Workup

  1. customThe cooling bath was removed
  2. customto attain room temperature
  3. temperaturebefore re-cooling to −78° C.
  4. stirringto stir 30 minutes at −78° C.
  5. customThe aqueous phase was separated
  6. extractionextracted with ethyl acetate (3×30 mL)
  7. washThe combined organic phases were washed twice with 10% aqueous citric acid solution (30 mL), water (30 mL), brine (20 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by column chromatography (120 g silica gel column, hexanes/ethyl acetate gradient elution 100/0 to 0/100)
  12. customevaporated
  13. customThe residue was triturated with 10% tert-butyl methyl ether in hexanes
  14. filtrationthe resulting off-white solid collected by filtration
  15. washrinsed with hexanes and vacuum
  16. customdried

Sources & evidence

ORD record
ord-54e083dcca9e4c5cb1e08ad1f95ddd4a
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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