Potassium Carbonate → HCID 53993986, compound

HRID 2186721Notes

Reaction equation

HRID 2186721 reaction equation
[Cl:1][CH2:2][C:3]#[C:4][CH2:5]Cl.C([O-])([O-])=O.[K+].[K+].[F:13][C:14]([F:44])([F:43])[C:15]1[CH:16]=[C:17]([CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1)[C:18]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][C@H:21]1[CH2:26][C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[NH:29][CH:28]=1)=[O:19]>CN(C=O)C>[F:42][C:39]([F:40])([F:41])[C:37]1[CH:36]=[C:17]([CH:16]=[C:15]([C:14]([F:13])([F:43])[F:44])[CH:38]=1)[C:18]([N:20]1[CH2:25][CH2:24][N:23]([CH2:5][C:4]#[C:3][CH2:2][Cl:1])[CH2:22][C@H:21]1[CH2:26][C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[NH:29][CH:28]=1)=[O:19]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 131821,4-Dichloro-2-butyneHCID 10972505(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)piperazine

Product 1

HCID 53993986HCID 53993986, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

22 ml 1,4-dichloro-2-butine was added to a suspension of 43 g K2CO3 in 100 ml DMF at 20° C. under a protective gas atmosphere. The mixture was heated to 50° C. and then a solution of 50 g (2R)-1-[3,5-bis(trifluoromethyl)-benzoyl]-2-(1H-indol-3-ylmethyl)piperazine in 200 ml DMF was added dropwise to this receiving solution. The resulting mixture was stirred for 5 hours at 50° C. Stirring was continued overnight at room temperature, undissolved precipitate was filtered out, and the precipitate was washed twice with 200 ml portions of ethyl acetate. The combined filtrates were evaporated to dryness in a vacuum, and the resulting oil was purified by column chromatography (silica gel; mobile solvent: n-hexane/ethyl acetate 60/40 to 30/70). The combined product fractions were again evaporated to dryness. 40.4 g of (2R)-1-[3,5-bis(trifluoromethyl)-benzoyl]2-(1H-indol-3-ylmethyl]-4-(4-chloro-2-butin-1-yl)piperazine was obtained as an amorphous yellowish solid, which was used for the next synthesis stage without further purification.

Workup

  1. stirringStirring
  2. waitwas continued overnight at room temperature
  3. filtrationundissolved precipitate was filtered out
  4. washthe precipitate was washed twice with 200 ml portions of ethyl acetate
  5. customThe combined filtrates were evaporated to dryness in a vacuum
  6. customthe resulting oil was purified by column chromatography (silica gel; mobile solvent: n-hexane/ethyl acetate 60/40 to 30/70)
  7. customThe combined product fractions were again evaporated to dryness

Sources & evidence

ORD record
ord-a7af115a6a574ce293b9310299c8c6ab
Source dataset
uspto-grants-2002_06
Patent number
US06407106B1

Reaction notes

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