Triethylsilane → ethyl 2-(2-(2-hydroxyethyl)-3,5-dimethyl-4-(4-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetate

HRID 1189567Notes

Reaction equation

HRID 1189567 reaction equation
FC(F)(F)S(O[Si](C)(C)C)(=O)=O.[CH3:13][C:14]1[N:18]([CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:17]2[CH2:25][CH2:26][O:27][CH2:28][C:16]=2[CH:15]=1.[N:29]1([S:34]([C:37]2[CH:44]=[CH:43][C:40]([CH:41]=O)=[CH:39][CH:38]=2)(=[O:36])=[O:35])[CH2:33][CH2:32][CH2:31][CH2:30]1.C([SiH](CC)CC)C>C(Cl)Cl>[OH:27][CH2:26][CH2:25][C:17]1[N:18]([CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:14]([CH3:13])=[C:15]([CH2:41][C:40]2[CH:43]=[CH:44][C:37]([S:34]([N:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)(=[O:36])=[O:35])=[CH:38][CH:39]=2)[C:16]=1[CH3:28]

Participants

6

Reactant 4

HCID 12052TriethylsilaneHCID 65367Trimethylsilyl triflateHCID 58310957ethyl 2-(2-methyl-6,7-dihydropyrano[4,3-b]pyrrol-1(4H)-yl)acetateHCID 585641144-(Pyrrolidine-1-sulfonyl)benzaldehyde

Product 1

HCID 58310958ethyl 2-(2-(2-hydroxyethyl)-3,5-dimethyl-4-(4-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetateYield 33.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a flame-dried vial was charged with DCM (2 ml) and trimethylsilyl trifluoromethanesulfonate (0.081 ml, 0.448 mmol) was added at 0° C., followed by a solution of ethyl 2-(2-methyl-6,7-dihydropyrano[4,3-b]pyrrol-1(4H)-yl)acetate (50 mg, 0.224 mmol) and 4-(pyrrolidin-1-ylsulfonyl)benzaldehyde (53.6 mg, 0.224 mmol) in CH2Cl2 (5 ml) (cannulated), the mix was stirred at 0° C. for 15 min, neat triethylsilane (0.143 ml, 0.896 mmol) was added slowly, stirred for 30 min at 0° C., then slowly warmed to r.t. TLC confirmed that reaction was done. Therefore, it was quenched with sat. NaHCO3, extracted with DCM. Combined DCM was dried with Na2SO4, filtered and concentrated under vacuum. The residue was chromatographed on silica using a Biotage automated system (5-30-50% ethyl acetate/hexanes) to give ethyl 2-(2-(2-hydroxyethyl)-3,5-dimethyl-4-(4-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetate (34 mg, 0.076 mmol, 33.8% yield).

Workup

  1. additionwas added at 0° C.
  2. stirringstirred for 30 min at 0° C.
  3. temperatureslowly warmed to r.t
  4. customTLC confirmed that reaction
  5. customTherefore, it was quenched with sat. NaHCO3
  6. extractionextracted with DCM
  7. dry with materialCombined DCM was dried with Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customThe residue was chromatographed on silica using a Biotage

Sources & evidence

ORD record
ord-81b88e78c53349f5af8f990a2f92b4db
Source dataset
uspto-grants-2014_03
Patent number
US08674115B2

Reaction notes

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