Hydrochloric Acid → 5-Methyl-3-phenylisoxazole-4-carboxylic acid [4-dimethylamino-4-(3-fluorophenyl)cyclohexyl]amide hydrochloride

HRID 418316

Reaction equation

HRID 418316 reaction equation
FC1C=C(C2(N(C)C)CCC(N)CC2)C=CC=1.CC1ON=C(C2C=CC=CC=2)C=1C(O)=O.Cl.[CH3:34][N:35]([CH3:64])[C:36]1([C:57]2[CH:62]=[CH:61][CH:60]=[C:59]([F:63])[CH:58]=2)[CH2:41][CH2:40][CH:39]([NH:42][C:43]([C:45]2[C:46]([C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)=[N:47][O:48][C:49]=2[CH3:50])=[O:44])[CH2:38][CH2:37]1.[Cl:65][Si](C)(C)C>CC(=O)CC.O.C(OCC)(=O)C.CO.C(OCC)C.CO.C(OCC)C>[ClH:65].[CH3:64][N:35]([CH3:34])[C:36]1([C:57]2[CH:62]=[CH:61][CH:60]=[C:59]([F:63])[CH:58]=2)[CH2:37][CH2:38][CH:39]([NH:42][C:43]([C:45]2[C:46]([C:51]3[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=3)=[N:47][O:48][C:49]=2[CH3:50])=[O:44])[CH2:40][CH2:41]1

Participants

12

Reactant 5

HCID 313Hydrochloric AcidHCID 6397ChlorotrimethylsilaneHCID 143435-Methyl-3-phenylisoxazole-4-carboxylic acidHCID 579041991-(3-fluorophenyl)-N,N-dimethylcyclohexane-1,4-diamineHCID 666515355-Methyl-3-phenylisoxazole-4-carboxylic acid [4-dimethylamino-4-(3-fluorophenyl)cyclohexyl]amide

Product 1

HCID 666516395-Methyl-3-phenylisoxazole-4-carboxylic acid [4-dimethylamino-4-(3-fluorophenyl)cyclohexyl]amide hydrochloride

Reagents, catalysts & solvents 6

HCID 887MethanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6569Methyl Ethyl KetoneSolventHCID 8857Ethyl AcetateSolventHCID 21864698Diethyl ether methanolSolvent2×

Procedure

As described for Example 120, 700 mg of a cis-trans mixture of 1-(3-fluorophenyl)-N,N-dimethylcyclohexane-1,4-diamine were reacted with 600 mg 5-methyl-3-phenylisoxazole-4-carboxylic acid (1 molar equivalent) and the crude product was isolated. The main fraction, obtained after column chromatography on silica gel (3.0×19 cm) with 175 ml diethyl ether followed by 250 ml diethyl ether/methanol (V:V=2:1), 250 ml diethyl ether/methanol (V:V=1:1) and 200 ml methanol, of 775 mg was dissolved in 10 ml 2-butanone and 10 ml ethyl acetate and converted into the corresponding hydrochloride of the non-polar diastereoisomer of 5-methyl-3-phenylisoxazole-4-carboxylic acid [4-dimethylamino-4-(3-fluorophenyl)cyclohexyl]amide by adding 33 μl water and 233 μl chlorotrimethylsilane (423 mg of white solid, Mp. 256-259° C.).

Workup

  1. customthe crude product was isolated

Sources & evidence

ORD record
ord-e8b5abc0164a451394ad1fff15b0e26c
Source dataset
uspto-grants-2012_01
Patent number
US08093272B2

Linked notes

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