Sodium Sulfide → HCID 69883845, compound

HRID 2120364Notes

Reaction equation

HRID 2120364 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([S:9][C:10]#N)[CH:5]=[CH:4][C:3]=1[NH:12][C:13](=[O:21])[C@:14]([OH:20])([CH3:19])[C:15]([F:18])([F:17])[F:16].[S-2].[Na+].[Na+].[CH3:25][N:26]([CH3:36])[C:27]([C:29]1[CH:34]=[CH:33]C(I)=[CH:31][CH:30]=1)=[O:28]>CN(C=O)C.O>[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([S:9][C:10]2[CH:33]=[CH:34][C:29]([C:27](=[O:28])[N:26]([CH3:36])[CH3:25])=[CH:30][CH:31]=2)[CH:5]=[CH:4][C:3]=1[NH:12][C:13](=[O:21])[C@:14]([OH:20])([CH3:19])[C:15]([F:18])([F:17])[F:16]

Participants

6

Reactant 3

HCID 14804Sodium SulfideHCID 8799334-iodo-N,N-dimethylbenzamideHCID 20621499HCID 20621499, compound

Product 1

HCID 69883845HCID 69883845, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

(R)-N[2,3-Dichloro-4-thiocyanatophenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Method 39) (0.5 g) as a solution in DMF was treated with a solution of sodium sulphide (403 mg) in water (2 ml) and the mixture was heated at 50° C. for 1 hour. The reaction mixture was then treated with a solution of N,N-dimethylcarbamoyl-4-iodobenzene (0.455 g) in DMF (5 ml), followed by cuprous oxide (0.121 g). The reaction mixture was heated at 150° C. for 4.5 hours under an argon atmosphere. The reaction mixture was quenched with water (100 ml), and DCM was added (100 ml) and the mixture was filtered through diatomaceous earth. The aqueous layer was separated and washed with DCM (3×50 ml). The organic extracts were combined and dried. The volatile material was removed by evaporation, and the product was purified by chromatography using a Mega Bond Elut column (20 g silica) eluting with 0-5% MeOH/DCM to yield the title compound as a white solid. (0.53 g) 80%. NMR: 1.60 (s, 3H), 2.95 (d, 6H), 7.30 (d, 1H); 7.30-7.50 (m, 4H), 7.85 (s, 1H), 7.90 (d, 1H), 9.90 (s, 1H); m/z: 479.

Workup

  1. temperatureThe reaction mixture was heated at 150° C. for 4.5 hours under an argon atmosphere
  2. customThe reaction mixture was quenched with water (100 ml), and DCM
  3. additionwas added (100 ml)
  4. filtrationthe mixture was filtered through diatomaceous earth
  5. customThe aqueous layer was separated
  6. washwashed with DCM (3×50 ml)
  7. customdried
  8. customThe volatile material was removed by evaporation
  9. customthe product was purified by chromatography
  10. washeluting with 0-5% MeOH/DCM

Sources & evidence

ORD record
ord-c72fe7e7f8c746cfa2177438376537ab
Source dataset
uspto-grants-2004_02
Patent number
US06689909B1

Reaction notes

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