Lawesson's reagent → Tert-butyl 10-(5-methylthiazol-2-yl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

HRID 72881Notes

Reaction equation

HRID 72881 reaction equation
[CH2:1]([NH:5][C:6]([CH:8]1[O:25][C:12]2([CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)[CH2:11][N:10]([CH2:26][C:27]([F:30])([F:29])[F:28])[CH2:9]1)=O)[C:2]([CH3:4])=O.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:40])=CC=1>C1COCC1>[CH3:4][C:2]1[S:40][C:6]([CH:8]2[O:25][C:12]3([CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[CH2:11][N:10]([CH2:26][C:27]([F:30])([F:29])[F:28])[CH2:9]2)=[N:5][CH:1]=1

Participants

4

Reactant 2

HCID 87949Lawesson's reagentHCID 70872681Tert-butyl 10-(acetonylcarbamoyl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

Product 1

HCID 70872713Tert-butyl 10-(5-methylthiazol-2-yl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylateYield 121.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

Tert-butyl 10-(acetonylcarbamoyl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (80 mg, 0.18 mmol) was dissolved in anhydrous THF (1.5 mL) followed by the addition of Lawesson's reagent (114 mg, 0.27 mmol) and the reaction mixture was heated at 70° C. for 1 hour under an atmosphere of nitrogen. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography using 0-10% EtOAc in DCM as eluent to yield tert-butyl 10-(5-methylthiazol-2-yl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (95 mg, 100%). ESI-MS m/z calc. 435.5. Found 436.5 (M+1)+; Retention time: 1.67 minutes (3 min run); 1H NMR (400 MHz, CDCl3) δ 7.54 (s, 1H), 5.20 (dd, J=9.4, 0.8 Hz, 1H), 3.82-3.76 (m, 2H), 3.43 (d, J=10.1 Hz, 1H), 3.31-3.21 (m, 1H), 3.09-2.94 (m, 3H), 2.72 (dd, J=11.4, 0.5 Hz, 1H), 2.50 (s, 1H), 2.46 (s, 3H), 2.45-2.38 (m, 2H), 1.79-1.67 (m, 1H), 1.65-1.57 (m, 1H), 1.53 (dd, J=11.2, 4.8 Hz, 1H), 1.45 (s, 9H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customthe solvent was removed under reduced pressure
  3. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-13efa52327e64efdaf6c1f148e977df5
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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