Triethylamine → HCID 131732377, compound

HRID 921645Notes

Reaction equation

HRID 921645 reaction equation
FC(F)(F)S([O:6][Si:7]([CH:14]([CH3:16])[CH3:15])([CH:11]([CH3:13])[CH3:12])[CH:8]([CH3:10])[CH3:9])(=O)=O.[Cl:19][C:20]1[C:25]([NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[CH:24][C:23]([C:34]#[N:35])=[CH:22][C:21]=1[N:36]1[CH2:41][CH2:40][C@@H:39]([NH:42][C:43](=[O:45])[O-:44])[C@H:38](O)[CH2:37]1.[CH2:47](N(CC)CC)C>ClCCl>[Cl:19][C:20]1[C:25]([NH:26][C:27]([O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:28])=[CH:24][C:23]([C:34]#[N:35])=[CH:22][C:21]=1[N:36]1[CH2:37][CH2:38][C@@H:39]([NH:42][C:43](=[O:45])[O:44][CH3:47])[C@H:40]([O:6][Si:7]([CH:14]([CH3:16])[CH3:15])([CH:11]([CH3:13])[CH3:12])[CH:8]([CH3:10])[CH3:9])[CH2:41]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2724529Triisopropylsilyl trifluoromethanesulfonateHCID 131732378HCID 131732378, compound

Product 1

HCID 131732377HCID 131732377, compoundYield 118%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triisopropylsilyl trifluoromethanesulfonate (0.288 mL, 1.060 mmol) was added to a solution of ((3R,4R)-1-(2-chloro-5-cyano-3-(N-Boc-amino)phenyl)-3-hydroxypiperidin-4-yl)carbamate (150 mg, 0.353 mmol) and triethylamine (0.196 mL, 1.412 mmol) in dichloromethane (5 mL) and the resulting mixture was stirred at room temperature overnight. The reaction mixture was partitioned between saturated sodium bicarbonate and dichloromethane. The layers were separated and aqueous layer was extracted with dichloromethane two more times. The combined organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel using an automated ISCO system (40 g column, eluting with 0-10% ethyl acetate/dichloromethane). Methyl ((3R,4R)-1-(2-chloro-5-cyano-3-(N-Boc-amino)phenyl)-3-((triisopropylsilyl)oxy) piperidin-4-yl)carbamate (242 mg) was obtained as a brown oil.

Workup

  1. customThe reaction mixture was partitioned between saturated sodium bicarbonate and dichloromethane
  2. customThe layers were separated
  3. extractionaqueous layer was extracted with dichloromethane two more times
  4. dry with materialThe combined organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography on silica gel using
  8. washan automated ISCO system (40 g column, eluting with 0-10% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-c66ac24d7ad04da88fb4a4f6395865c5
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

Loading…