Trifluoroacetic acid → Isopropyl 4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

HRID 1518427Notes

Reaction equation

HRID 1518427 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH:16]=[CH:15][C:14]([O:17][CH:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27](C)([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]3)=[CH:13][C:12]2=[O:31])=[CH:7][CH:6]=1)(=[O:4])=[O:3].C(O)(C(F)(F)F)=O.CCN(CC)CC.ClC(OC(C)C)=O>C(Cl)Cl>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH:16]=[CH:15][C:14]([O:17][CH:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][CH:27]([CH3:28])[CH3:29])=[O:25])[CH2:20][CH2:19]3)=[CH:13][C:12]2=[O:31])=[CH:7][CH:6]=1)(=[O:3])=[O:4]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 25204174Tert-butyl 4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Product 1

HCID 25138357Isopropyl 4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (53 mg, 0.118 mmol) in CH2Cl2 (1.0 mL) was added TFA (0.5 mL) dropwise. The reaction mixture was stirred for 1 h and evaporated under reduced pressure. The residue was then dissolved in CH2Cl2 (1.5 mL) followed by addition of Et3N (82 μL, 0.59 mmol) and isopropyl chloroformate (0.295 mL, 0.295 mmol, Aldrich). The resulting mixture was stirred at room temperature for 30 min, quenched with H2O (0.2 mL) and then evaporated to dryness. The crude product was purified by preparative HPLC (C18 column; 10-100% methanol in water containing 0.05% trifluoroacetic acid) to give Example 3 (44.5 mg, white solid, 87%) upon lyophilization. 1H NMR (500 MHz, CDCl3) δ 8.09 (d, J=8.80 Hz, 2 H), 7.61 (d, J=8.25 Hz, 2 H), 7.30 (d, J=7.70 Hz, 1 H), 6.28 (d, J=2.20 Hz, 1H), 6.19 (dd, J=7.70, 2.20 Hz, 1 H), 4.86-5.00 (m, 1 H), 4.51-4.63 (m, 1 H), 3.77 (app brs, 2 H), 3.33-3.44 (m, 2 H), 3.11 (s, 3 H), 1.96-2.11 (m, 2 H), 1.73-1.86 (m, J=7.15 Hz, 2 H), 1.26 (d, J=6.05 Hz, 6 H). MS (ESI) 435 (M+H).

Workup

  1. customevaporated under reduced pressure
  2. dissolutionThe residue was then dissolved in CH2Cl2 (1.5 mL)
  3. stirringThe resulting mixture was stirred at room temperature for 30 min
  4. customquenched with H2O (0.2 mL)
  5. customevaporated to dryness
  6. customThe crude product was purified by preparative HPLC (C18 column; 10-100% methanol in water containing 0.05% trifluoroacetic acid)
  7. customto give Example 3 (44.5 mg, white solid, 87%) upon lyophilization

Sources & evidence

ORD record
ord-77934dbb845642c68f00c254ee7ac0ef
Source dataset
uspto-grants-2012_07
Patent number
US08232404B2

Reaction notes

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