4-Methylpiperidine → HCID 49783917, compound

HRID 1946849Notes

Reaction equation

HRID 1946849 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:13][C:14]2[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=2[Cl:21])=[C:7]([S:9](Cl)(=[O:11])=[O:10])[CH:8]=1)#[N:2].[CH3:22][CH:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>C(Cl)Cl>[Cl:21][C:15]1[CH:16]=[CH:17][C:18]([Cl:20])=[CH:19][C:14]=1[O:13][C:6]1[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][C:7]=1[S:9]([N:26]1[CH2:27][CH2:28][CH:23]([CH3:22])[CH2:24][CH2:25]1)(=[O:11])=[O:10]

Participants

4

Reactant 2

HCID 693814-MethylpiperidineHCID 59548939HCID 59548939, compound

Product 1

HCID 49783917HCID 49783917, compoundYield 71.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Sulfonyl chloride 36 (0.20 g, 0.55 mmol) was combined with 4-methylpiperidine (0.16 g, 1.65 mmol) and TEA (0.17 g, 1.65 mmol) in DCM (5 mL). The solution was stirred overnight at room temperature. Upon consumption of starting material, as determined via TLC (75% EtOAc in hexanes), the reaction mixture was partitioned between DCM and water. After 3 extractions, the combined organic extracts were washed sequentially with saturated aqueous NaHCO3, water, and brine. The crude product was chromatographed on normal-phase silica to yield the desired product 87 (0.167 g, 71.4% yield, 97.1% pure). 1H NMR (500 MHz, DMSO-d6): δ 8.28 (d, J=2 Hz, 1H), 8.07 (dd, J1=9 Hz, J2=2 Hz, 1H), 7.72 (d, J=8 Hz, 1H), 7.46 (dd, J1=5 Hz, J2=2 Hz, 1H), 7.44 (d, J=2 Hz, 1H), 7.10 (d, J=9 Hz, 1H), 3.70 (d, J=12 Hz, 2H), 2.74 (ddd, J1=J2=12 Hz, J3=2 Hz, 2H), 1.65 (dd, J1=13 Hz, J2=2 Hz, 2H), 1.44 (m, 1H), 1.09 (ddd, J1=28 Hz, J2=13 Hz, J3=4 Hz, 2H), 0.87 (d, J=7 Hz, 3H); MS (ESI, EI+): m/z=425.11 (MH+); melting point: 127-130° C.

Workup

  1. customUpon consumption of starting material
  2. customthe reaction mixture was partitioned between DCM and water
  3. extractionAfter 3 extractions
  4. washthe combined organic extracts were washed sequentially with saturated aqueous NaHCO3, water, and brine
  5. customThe crude product was chromatographed on normal-phase silica

Sources & evidence

ORD record
ord-b621fb8477c047bd95cbd960c0a60fc7
Source dataset
uspto-grants-2013_03
Patent number
US08399456B2

Reaction notes

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