Trifluoroacetic acid → 1-[4-(3-Chlorophenyl)-4-(2-pyrrolidin-1-yl-ethoxy)-piperidin-1-yl]-2-[[(2S)-1-[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]-piperidin-2-yl]-methoxy]-ethanone

HRID 1881696Notes

Reaction equation

HRID 1881696 reaction equation
[CH3:1][CH2:2][N:3]([CH:7]([CH3:9])C)[CH:4]([CH3:6])C.[CH3:10][O:11][C:12]1[CH:17]=[C:16]([CH3:18])[C:15]([S:19]([N:22]2[CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]2[CH2:28][O:29][CH2:30][C:31]([OH:33])=O)(=[O:21])=[O:20])=[C:14]([CH3:34])[CH:13]=1.[CH:35]1[CH:36]=[CH:37][C:38]2N(O)N=N[C:39]=2[CH:40]=1.[CH3:45][CH2:46][N:47]=[C:48]=NCCCN(C)C.[ClH:56].[C:57]([OH:63])([C:59](F)(F)F)=O>C(Cl)Cl>[Cl:56][C:35]1[CH:40]=[C:39]([C:57]2([O:63][CH2:9][CH2:7][N:3]3[CH2:2][CH2:1][CH2:6][CH2:4]3)[CH2:45][CH2:46][N:47]([C:31](=[O:33])[CH2:30][O:29][CH2:28][C@@H:23]3[CH2:24][CH2:25][CH2:26][CH2:27][N:22]3[S:19]([C:15]3[C:14]([CH3:34])=[CH:13][C:12]([O:11][CH3:10])=[CH:17][C:16]=3[CH3:18])(=[O:20])=[O:21])[CH2:48][CH2:59]2)[CH:38]=[CH:37][CH:36]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57819715(S)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid

Product 1

HCID 444658841-[4-(3-Chlorophenyl)-4-(2-pyrrolidin-1-yl-ethoxy)-piperidin-1-yl]-2-[[(2S)-1-[(4-methoxy-2,6-dimethyl-phenyl)sulfonyl]-piperidin-2-yl]-methoxy]-ethanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Procedure

DIPEA (2.5 eq.) was added to a cooled solution (0° C.) of (S)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid [acid D] in methylene chloride (5 ml/mmol), followed by HOBt (1 eq.) and EDCl (1.5 eq.). The reaction mixture was stirred at room temperature for 10 min and cooled to 0° C. and a solution of Boc-deprotected tert-butyl 4-(3-chlorophenyl)-4-(2-(pyrrolidin-1-yl)ethoxy)piperidine-1-carboxylate [amine I] (1.2 eq.) [Boc-deprotected in the presence of TFA (10-13 eq.) in methylene chloride (see e.g. stage (iii)/amine H)] in methylene chloride was added. The reaction mixture was then stirred at room temperature for 16 h. In this time, the reaction reacted completely (TLC control). The reaction mixture was diluted with methylene chloride (20 ml) and washed with saturated ammonium chloride solution, saturated sodium chloride solution, saturated sodium bicarbonate solution and finally with sat. sodium chloride solution again. The organic phase was dried over sodium sulfate and concentrated to dryness on a rotary evaporator. The crude product was purified by means of column chromatography (silica gel, 2% methanol in methylene chloride).

Workup

  1. temperaturecooled to 0° C.
  2. stirringThe reaction mixture was then stirred at room temperature for 16 h
  3. customIn this time, the reaction reacted completely (TLC control)
  4. washwashed with saturated ammonium chloride solution, saturated sodium chloride solution, saturated sodium bicarbonate solution and finally with sat. sodium chloride solution again
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. concentrationconcentrated to dryness on a rotary evaporator
  7. customThe crude product was purified by means of column chromatography (silica gel, 2% methanol in methylene chloride)

Sources & evidence

ORD record
ord-dd203561d9ed4172a43957df7085e690
Source dataset
uspto-grants-2012_11
Patent number
US08318769B2

Reaction notes

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