Chlorotrimethylsilane → N-(2-(2-(4-Hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide hydrochloride

HRID 2041091Notes

Reaction equation

HRID 2041091 reaction equation
COC1C=C(C)C(S(N(CCOCC(O)=O)C)(=O)=O)=C(C)C=1.N1C=CC=C(C2(O)CCNCC2)C=1.C(=O)(O)[O-].[Na+].[OH:41][C:42]1([C:69]2[CH:70]=[N:71][CH:72]=[CH:73][CH:74]=2)[CH2:47][CH2:46][N:45]([C:48](=[O:68])[CH2:49][O:50][CH2:51][CH2:52][N:53]([CH3:67])[S:54]([C:57]2[C:62]([CH3:63])=[CH:61][C:60]([O:64][CH3:65])=[CH:59][C:58]=2[CH3:66])(=[O:56])=[O:55])[CH2:44][CH2:43]1.[Cl:75][Si](C)(C)C>C(Cl)Cl.C(OCC)C.C(C(C)=O)C>[ClH:75].[OH:41][C:42]1([C:69]2[CH:70]=[N:71][CH:72]=[CH:73][CH:74]=2)[CH2:43][CH2:44][N:45]([C:48](=[O:68])[CH2:49][O:50][CH2:51][CH2:52][N:53]([CH3:67])[S:54]([C:57]2[C:58]([CH3:66])=[CH:59][C:60]([O:64][CH3:65])=[CH:61][C:62]=2[CH3:63])(=[O:55])=[O:56])[CH2:46][CH2:47]1

Participants

8

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 516892Sodium BicarbonateHCID 49891674-(Pyridin-3-yl)piperidin-4-olHCID 25008578N-(2-(2-(4-Hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamideHCID 46870354{2-[(4-methoxy-2,6-dimethyl-benzenesulfonyl)-methyl-amino]-ethoxy}acetic Acid

Product 1

HCID 25008577N-(2-(2-(4-Hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide hydrochloride

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 19800284Diethyl ether 2-butanoneSolvent

Procedure

N,N′-Carbonyldiimidazole (77 mg, 0.475 mmol) was added to a solution of 2-(2-(4-methoxy-N,2,6-trimethylphenylsulfonamido)ethoxy)acetic acid (acid unit S2) (150 mg, 0.453 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) (80 mg, 0.453 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 (20 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 diethyl ether/methylene chloride/methanol/ammonia solution (25% aq.) (50:50:5:1). N-(2-(2-(4-Hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide (170 mg. 0.346 mmol) was dissolved in diethyl ether/methyl ethyl ketone (15:1, 32 ml), and chlorotrimethylsilane (81 μl, 0.692 mmol) was slowly added. The mixture was subsequently stirred for 30 min at 0° C. The precipitate formed was filtered off, washed with diethyl ether/hexane and dried.

Workup

  1. stirringthe reaction mixture was stirred for 15 h at room temperature
  2. extractionthe aqueous phase was subsequently extracted with methylene chloride (20 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 diethyl ether/methylene chloride/methanol/ammonia solution (25% aq.) (50:50:5:1)
  7. stirringThe mixture was subsequently stirred for 30 min at 0° C
  8. customThe precipitate formed
  9. filtrationwas filtered off
  10. washwashed with diethyl ether/hexane
  11. customdried

Sources & evidence

ORD record
ord-4ec8481045f14a3cb95c7c4c272523e5
Source dataset
uspto-grants-2013_11
Patent number
US08580965B2

Reaction notes

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