Methanesulfonamide → tert-Butyl-4-((4-chlorophenethyl)(4-((methylsulfonyl)carbamoyl)benzyl)amino)-piperidine-1-carboxylate

HRID 59797Notes

Reaction equation

HRID 59797 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH2:24][C:25]2[CH:33]=[CH:32][C:28]([C:29]([OH:31])=O)=[CH:27][CH:26]=2)[CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[CH3:43][S:44]([NH2:47])(=[O:46])=[O:45].CN(C(F)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[CH2:24][C:25]2[CH:26]=[CH:27][C:28]([C:29](=[O:31])[NH:47][S:44]([CH3:43])(=[O:46])=[O:45])=[CH:32][CH:33]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 4

HCID 72879MethanesulfonamideHCID 81531DiisopropylethylamineHCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 1214102754-(((1-(Tert-butoxycarbonyl)piperidin-4-yl)(4-chlorophenethyl)amino)methyl)benzoic acid

Product 1

HCID 121410313tert-Butyl-4-((4-chlorophenethyl)(4-((methylsulfonyl)carbamoyl)benzyl)amino)-piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

4-(((1-(tert-Butoxycarbonyl)piperidin-4-yl)(4-chlorophenethyl)amino)methyl)benzoic acid synthesized in Step 2 was dissolved in DCM (5 mL/mmol) and DIPEA (3 equiv) and methanesulfonamide (2 eqs) were added. The reaction mixture was cooled to 0° C. and TFFH (1.2 eq) was added in one portion. The reaction mixture was stirred at 0° C. for 6 hours and then for 15 hours at room temperature. Ethyl acetate (15 mL/mmol) was added and the solution was washed sequentially with 5% citric acid (2×), 5% NaHCO3 (2×) and brine (2×) and was dried over MgSO4. The drying agent was filtered off and the solvents were evaporated in vacuo. The crude product was purified by silica gel chromatography.

Workup

  1. waitfor 15 hours at room temperature
  2. washthe solution was washed sequentially with 5% citric acid (2×), 5% NaHCO3 (2×) and brine (2×)
  3. dry with materialwas dried over MgSO4
  4. filtrationThe drying agent was filtered off
  5. customthe solvents were evaporated in vacuo
  6. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-fafa4e02f7954352b8db3cbd71eacd43
Source dataset
uspto-grants-2016_09
Patent number
US09440953B2

Reaction notes

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