Triethylamine → 2,2,2-trifluoro-N-[4-(1-piperidinesulfonylpiperidin-4-ylmethyl)-phenyl]acetamide

HRID 1358847Notes

Reaction equation

HRID 1358847 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[CH:8][CH:7]=1)=[O:4].C(N(CC)CC)C.[N:28]1([S:34](Cl)(=[O:36])=[O:35])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1>ClCCl>[F:20][C:2]([F:1])([F:19])[C:3]([NH:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:12][CH:13]2[CH2:14][CH2:15][N:16]([S:34]([N:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)(=[O:36])=[O:35])[CH2:17][CH2:18]2)=[CH:10][CH:11]=1)=[O:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 11298344Piperidine-1-sulfonyl chlorideHCID 218767392,2,2-trifluoro-N-(4-(piperidin-4-ylmethyl)-phenyl]acetamide

Product 1

HCID 120943982,2,2-trifluoro-N-[4-(1-piperidinesulfonylpiperidin-4-ylmethyl)-phenyl]acetamideYield 63.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
2.5 °C

Procedure

A solution of 2,2,2-trifluoro-N-[4-(piperidin-4-ylmethyl)-phenyl]acetamide (0.5 g, 1.75 mmol) (prepared as previously described in Example 19, steps 1 to 3) and triethylamine in dichloromethane (10 mL) was cooled in an ice bath under a nitrogen atmosphere. The mixture was then treated with a solution of 1-piperidinesulfonyl chloride (0.39 g, 2.09 mmol) in dichloromethane (1 mL). The reaction mixture was stirred for 1.5 hours at 0-5° C. and quenched with water. The organic layer was separated, and the aqueous layer extracted with dichloromethane. The combined organic extracts were washed with water and brine, dried, and solvents removed in vacuo. The residue was chromatographed on silica gel, eluting with 30% ethyl acetate/hexanes, to give 2,2,2-trifluoro-N-[4-(1-piperidinesulfonylpiperidin-4-ylmethyl)-phenyl]acetamide (0.48 g) as a white solid, m.p. 156-157° C.; Analysis for C19H26N3O3SF3: Calc.: C, 52.64; H, 6.05; N, 9.69; Found: C, 52.84; H, 6.00; N, 9.79.

Workup

  1. temperaturewas cooled in an ice bath under a nitrogen atmosphere
  2. customquenched with water
  3. customThe organic layer was separated
  4. extractionthe aqueous layer extracted with dichloromethane
  5. washThe combined organic extracts were washed with water and brine
  6. customdried
  7. customsolvents removed in vacuo
  8. customThe residue was chromatographed on silica gel
  9. washeluting with 30% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-f50404ad1fb54006937e8b2069844b35
Source dataset
uspto-grants-2003_07
Patent number
US06596876B2

Reaction notes

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