2,2,2-Trifluoroethyl trifluoromethanesulfonate → (4-Isopropoxy-3-methyl-phenyl)-[10-(5-methyloxazol-2-yl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone

HRID 73022Notes

Reaction equation

HRID 73022 reaction equation
Cl.[CH:2]([O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([N:14]2[CH2:19][CH2:18][C:17]3([O:24][CH:23]([C:25]4[O:26][C:27]([CH3:30])=[CH:28][N:29]=4)[CH2:22][NH:21][CH2:20]3)[CH2:16][CH2:15]2)=[O:13])=[CH:8][C:7]=1[CH3:31])([CH3:4])[CH3:3].FC(F)(F)S(O[CH2:38][C:39]([F:42])([F:41])[F:40])(=O)=O.C([O-])(O)=O.[Na+]>CCO>[CH:2]([O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([N:14]2[CH2:19][CH2:18][C:17]3([O:24][CH:23]([C:25]4[O:26][C:27]([CH3:30])=[CH:28][N:29]=4)[CH2:22][N:21]([CH2:38][C:39]([F:42])([F:41])[F:40])[CH2:20]3)[CH2:16][CH2:15]2)=[O:13])=[CH:8][C:7]=1[CH3:31])([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 516892Sodium BicarbonateHCID 70872380HCID 70872380, compound

Product 1

HCID 66546983(4-Isopropoxy-3-methyl-phenyl)-[10-(5-methyloxazol-2-yl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanoneYield 9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (4-isopropoxy-3-methyl-phenyl)-[10-(5-methyloxazol-2-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone hydrochloride salt (32 mg, 0.07 mmol), 2,2,2-trifluoroethyl trifluoromethanesulfonate (17 μL, 0.11 mmol) and NaHCO3 (24 mg, 0.28 mmol) in anhydrous EtOH (800 μL) was heated at 80° C. in a sealed vial for 18 hours. The reaction mixture was allowed to cool to room temperature, microfiltered and purified by Waters mass directed LC/MS: (10-99% ACN/H2O (5 mM HCl)) and concentrated in vacuo to yield (4-isopropoxy-3-methyl-phenyl)-[10-(5-methyloxazol-2-yl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone (3 mg, 9%) as a white solid. ESI-MS m/z calc. 495.5. Found 496.7 (M+1)+; Retention time: 1.99 minutes (3 min run); 1H NMR (400 MHz, DMSO) δ 7.27-7.13 (m, 2H), 6.96 (d, J=9.0 Hz, 1H), 6.82 (d, J=1.2 Hz, 1H), 4.86 (dd, J=12.0, 4.7 Hz, 1H), 4.71-4.54 (m, 1H), 3.32-3.14 (m, 5H), 3.07 (dd, J=11.5, 2.6 Hz, 1H), 2.90-2.83 (m, 1H), 2.70 (dd, J=18.3, 7.2 Hz, 1H), 2.41-2.23 (m, 6H), 2.13 (s, 3H), 1.64-1.39 (m, 3H), 1.29 (d, J=6.0 Hz, 6H).

Workup

  1. temperatureto cool to room temperature
  2. custommicrofiltered and purified by Waters mass
  3. concentration(10-99% ACN/H2O (5 mM HCl)) and concentrated in vacuo

Sources & evidence

ORD record
ord-b9fe37c65283480380c66b4630a82158
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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