Hydrochloric Acid → HCID 68892678, compound

HRID 1454179Notes

Reaction equation

HRID 1454179 reaction equation
[Cl:1]C1C=CC(C(CCC(O)=O)=O)=CC=1.CN(C=O)C.[CH3:20][N:21]([CH3:35])[C:22]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:27][CH2:26][CH:25]([NH2:28])[CH2:24][CH2:23]1.ON1C2C=CC=CC=2N=N1.C(=O)([O-])[O-].[Na+].[Na+].Cl.[Cl:53][C:54]1[CH:59]=[CH:58][C:57]([C:60](=[O:81])[CH2:61][CH2:62][C:63](NC2CCC(N(C)C)(C3C=CC=CC=3)CC2)=[O:64])=[CH:56][CH:55]=1.Cl[Si](C)(C)C>C(OC(=O)C)C.O.C(OC(=O)C)C.C1COCC1>[ClH:1].[Cl:53][C:54]1[CH:55]=[CH:56][C:57]([C:60](=[O:81])[CH2:61][CH2:62][C:63]([NH:28][CH:25]2[CH2:26][CH2:27][C:22]([N:21]([CH3:35])[CH3:20])([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:23][CH2:24]2)=[O:64])=[CH:58][CH:59]=1

Participants

12

Reactant 8

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 6397ChlorotrimethylsilaneHCID 10340Sodium CarbonateHCID 757711-HydroxybenzotriazoleHCID 776043-(4-Chlorobenzoyl)propionic acidHCID 129862564-Dimethylamino-4-phenyl-cyclohexylamineHCID 68891977HCID 68891977, compound

Product 1

HCID 68892678HCID 68892678, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 21939870Tetrahydrofuran ethyl acetateSolvent

Procedure

310 mg 3-(4-chlorobenzoyl) propanoic acid (4-(4-chloro-phenyl)-4-oxobutyric acid, 1 mol equivalent) dissolved in 1.6 ml DMF (5 mol equivalents) were added to 350 mg of the non-polar diastereoisomer of N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, 230 Al N,N-diisopropylcarbodiimide (DIC, 1 mol equivalent) and 200 μg 1-hydroxybenzotriazole (HOBt, 1 mol equivalent) at 0° C. and while stirring. After three hours at this temperature, the mixture was stirred overnight while heating to room temperature. For working up, one-molar sodium carbonate solution was added (pH >10) and the crude product (855 mg) isolated by extraction with ethylacetate/THF (V:V=1:1), subsequent drying over sodium sulphate and evaporation. The main fraction of 447 mg obtained by column chromatography on silica gel (4.0×18 cm) with methanol/ethylacetate/n-hexane (V:V:V=1:1:1) was dissolved in 45 ml ethylacetate and was converted into the corresponding hydrochloride of the non-polar diastereoisomer of 4-(4-chloro-phenyl)-N-(4-dimethylamino-4-phenylcyclohexyl)-4-oxobutyramide) by adding 20 μl water and 140 μl chlorotrimethylsilane (353 mg white solid, mp. 177-180° C.).

Workup

  1. stirringthe mixture was stirred overnight
  2. dry with materialsubsequent drying over sodium sulphate and evaporation
  3. customThe main fraction of 447 mg obtained by column chromatography on silica gel (4.0×18 cm) with methanol/ethylacetate/n-hexane (V:V:V=1:1:1)

Sources & evidence

ORD record
ord-9493afc63c284ee4a7e416e8014be802
Source dataset
uspto-grants-2009_01
Patent number
US07476763B2

Reaction notes

Loading…