Hydrochloric Acid → HCID 86602699, compound

HRID 1375009Notes

Reaction equation

HRID 1375009 reaction equation
Br.Br.[CH3:3][O:4][C:5]1[CH:6]=[C:7]([CH:15]=[CH:16][C:17]=1[C:18]([F:21])([F:20])[F:19])[CH2:8][CH:9]1[CH2:14][NH:13][CH2:12][CH2:11][NH:10]1.[I-].[K+].C(N(CC)C(C)C)(C)C.Cl.[Cl:34][CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][O:40][C@@H:39]([CH2:43][O:44][CH3:45])[CH2:38]1.[F:46][C:47]([F:62])([F:61])[C:48]1[CH:49]=[C:50]([CH:54]=[C:55]([C:57]([F:60])([F:59])[F:58])[CH:56]=1)[C:51]([Cl:53])=[O:52].Cl>CN(C)C=O.C(OCC)(=O)C>[ClH:34].[ClH:53].[F:46][C:47]([F:61])([F:62])[C:48]1[CH:49]=[C:50]([CH:54]=[C:55]([C:57]([F:60])([F:58])[F:59])[CH:56]=1)[C:51]([N:10]1[CH2:11][CH2:12][N:13]([CH2:35][CH2:36][N:37]2[CH2:42][CH2:41][O:40][C@H:39]([CH2:43][O:44][CH3:45])[CH2:38]2)[CH2:14][CH:9]1[CH2:8][C:7]1[CH:15]=[CH:16][C:17]([C:18]([F:20])([F:21])[F:19])=[C:5]([O:4][CH3:3])[CH:6]=1)=[O:52]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 1018563,5-Bis(trifluoromethyl)benzoyl chlorideHCID 17963962HCID 17963962, compoundHCID 69417659HCID 69417659, compound

Product 1

HCID 86602699HCID 86602699, compoundYield 23.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a stirred suspension of 2-[3-methoxy-4-(trifluoromethyl)benzyl]piperazine dihydrobromide (109 mg), potassium iodide (109 mg) and N,N-diisopropylethylamine (0.26 ml) in N,N-dimethylformamide (4 ml) was added (2R)-4-(2-chloroethyl)-2-(methoxymethyl)morpholine hydrochloride (29 mg) at 5° C. under nitrogen atmosphere and the mixture was gradually warmed to room temperature overnight. To the above stirred suspension was added 3,5-bis(trifluoromethyl)-benzoyl chloride (118 mg) at 5° C. and the mixture was stirred for 1 hour at the same temperature. The mixture was extracted with ethyl acetate and the extract was washed with water, and dried over magnesium sulfate. The usual work up followed by flash chromatography on silica gel with a mixture of dichloromethane and methanol (60:1) gave the product, which was dissolved in ethyl acetate and treated with 4N hydrogen chloride in ethyl acetate to give 1-[3,5-bis(trifluoromethyl)benzoyl]-2-[3-methoxy-4-(trifluoromethyl)benzyl]-4-[2-[(2S)-2-(methoxymethyl)-morpholino]ethyl]piperazine dihydrochloride (22 mg) as a powder.

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washthe extract was washed with water
  3. dry with materialdried over magnesium sulfate
  4. additionThe usual work up followed by flash chromatography on silica gel with a mixture of dichloromethane and methanol (60:1)
  5. customgave the product, which

Sources & evidence

ORD record
ord-4f504468d2da4c45a53ba8f1356c30f8
Source dataset
uspto-grants-2007_01
Patent number
US07166598B2

Reaction notes

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