Chloroform → HCID 76618687, compound

HRID 1012202Notes

Reaction equation

HRID 1012202 reaction equation
[F:1][C:2]([F:37])([F:36])[C:3]1[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:4]=1[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]=[C:14]2[S:18][C:17]([N:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[N:16][C:15]2=[O:25])=[CH:9][C:8]=1[O:26][CH3:27].C(Cl)(Cl)Cl.[C:42](Cl)(=[O:44])[CH3:43]>CCOC(C)=O>[C:42]([N:22]1[CH2:21][CH2:20][N:19]([C:17]2[S:18][C:14](=[CH:13][C:10]3[CH:11]=[CH:12][C:7]([O:6][CH2:5][C:4]4[CH:28]=[CH:29][C:30]([C:32]([F:35])([F:33])[F:34])=[CH:31][C:3]=4[C:2]([F:36])([F:1])[F:37])=[C:8]([O:26][CH3:27])[CH:9]=3)[C:15](=[O:25])[N:16]=2)[CH2:24][CH2:23]1)(=[O:44])[CH3:43]

Participants

5

Reactant 3

HCID 6212ChloroformHCID 6367Acetyl chlorideHCID 730441835-[1-[4-(2,4-Bis-trifluoromethyl-benzyloxy)-3-methoxy-phenyl]-methylidene]-2-piperazin-1-yl-thiazol-4-one

Product 1

HCID 76618687HCID 76618687, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

To a flask was added 5-[1-[4-(2,4-bis-trifluoromethyl-benzyloxy)-3-methoxy-phenyl]-methylidene]-2-piperazin-1-yl-thiazol-4-one (51, mg, 94 μL) from Example 23, chloroform (5 mL), acetyl chloride (1.5 equiv, 10 μL) and TEA (3 equiv, 40 μL). The reaction solution was stirred at 45° C. for 1.5 hours. The solution was then diluted with EtOAc (75 mL) and filtered through a Buchner funnel to remove excess K2CO3. The solution was washed with aq NH4Cl (50 ml×2), dried over Na2SO4, filtered, and concentrated in vacuo. The crude material was chromatographed (SiO2, DCM/MeOH 100:0 to 94:06) to provide the title compound (19 mg, 40% yield). 1H NMR (CDCl3) δ 7.95-7.97 (2H, m), 7.84 (2H, d, J=7.7 Hz), 7.77 (1H, s), 7.08-7.11 (2H, m), 6.87 (1H, d, J=8.2 Hz), 5.44 (2H, s), 4.09-4.11 (2H, m), 3.97 (3H, s), 3.79-3.81 (2H, m), 3.61-3.66 (4H, m), 2.17 (3H, s), 1.60 (3H, s); MS (ESI) 588 (MH+).

Workup

  1. filtrationfiltered through a Buchner funnel
  2. customto remove excess K2CO3
  3. washThe solution was washed with aq NH4Cl (50 ml×2)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was chromatographed (SiO2, DCM/MeOH 100:0 to 94:06)

Sources & evidence

ORD record
ord-1cf16cac55de41088c45975941d170f1
Source dataset
uspto-grants-2011_07
Patent number
US07977489B2

Reaction notes

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