Chlorotrimethylsilane → 1-(4-Hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)ethanone hydrochloride

HRID 2041089Notes

Reaction equation

HRID 2041089 reaction equation
COC1C=C(C)C(S(N2CCCCC2COCC(O)=O)(=O)=O)=C(C)C=1.N1C=CC=C(C2(O)CCNCC2)C=1.C(=O)(O)[O-].[Na+].[OH:44][C:45]1([C:75]2[CH:76]=[N:77][CH:78]=[CH:79][CH:80]=2)[CH2:50][CH2:49][N:48]([C:51](=[O:74])[CH2:52][O:53][CH2:54][CH:55]2[CH2:60][CH2:59][CH2:58][CH2:57][N:56]2[S:61]([C:64]2[C:69]([CH3:70])=[CH:68][C:67]([O:71][CH3:72])=[CH:66][C:65]=2[CH3:73])(=[O:63])=[O:62])[CH2:47][CH2:46]1.[Cl:81][Si](C)(C)C>C(Cl)Cl.C(C(C)=O)C.C(OCC)C>[ClH:81].[OH:44][C:45]1([C:75]2[CH:76]=[N:77][CH:78]=[CH:79][CH:80]=2)[CH2:50][CH2:49][N:48]([C:51](=[O:74])[CH2:52][O:53][CH2:54][CH:55]2[CH2:60][CH2:59][CH2:58][CH2:57][N:56]2[S:61]([C:64]2[C:65]([CH3:73])=[CH:66][C:67]([O:71][CH3:72])=[CH:68][C:69]=2[CH3:70])(=[O:62])=[O:63])[CH2:47][CH2:46]1

Participants

9

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 516892Sodium BicarbonateHCID 49891674-(Pyridin-3-yl)piperidin-4-olHCID 247718541-(4-Hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)ethanoneHCID 574368002-((1-(4-Methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid

Product 1

HCID 247718531-(4-Hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)ethanone hydrochloride

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 6569Methyl Ethyl KetoneSolvent

Procedure

N,N′-Carbonyldiimidazole (68 mg, 0.424 mmol) was added to a solution of 2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid (150 mg, 0.404 mmol) in methylene chloride (5 ml) and the mixture was stirred for 1 h at room temperature. A solution of 4-(pyridin-3-yl)piperidin-4-ol (A2) (72 mg, 0.404 mmol) in methylene chloride (2 ml) was subsequently added and the reaction mixture was stirred for 15 h at room temperature. Thereafter, saturated sodium bicarbonate solution (10 ml) was added to the reaction mixture and the aqueous phase was subsequently extracted with methylene chloride (2×10 ml). The combined organic phases were extracted with saturated sodium chloride solution (10 ml), dried with sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography with ethyl acetate/methanol (20:1). 1-(4-Hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)ethanone (100 mg, 0.188 mmol) was dissolved in methyl ethyl ketone (3 ml), and chlorotrimethylsilane (28 μl, 0.226 mmol) was slowly added. Diethyl ether (10 ml) was subsequently added and the mixture was stirred for 1 h at 0° C. The precipitate formed was filtered off, dried with exclusion of air and washed with diethyl ether.

Workup

  1. stirringthe reaction mixture was stirred for 15 h at room temperature
  2. extractionthe aqueous phase was subsequently extracted with methylene chloride (2×10 ml)
  3. extractionThe combined organic phases were extracted with saturated sodium chloride solution (10 ml)
  4. dry with materialdried with sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography with ethyl acetate/methanol (20:1)
  7. stirringthe mixture was stirred for 1 h at 0° C
  8. customThe precipitate formed
  9. filtrationwas filtered off
  10. customdried with exclusion of air
  11. washwashed with diethyl ether

Sources & evidence

ORD record
ord-7419ec35648a445b9bec616d85415126
Source dataset
uspto-grants-2013_11
Patent number
US08580965B2

Reaction notes

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