2,2,2-Trifluoroethyl trifluoromethanesulfonate → HCID 66546983, compound

HRID 73040Notes

Reaction equation

HRID 73040 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:29]N=[C:27]([CH3:30])[N:26]=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:45]([O-])(O)=O.[Na+]>>[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:29][C:30]([CH3:45])=[CH:27][N:26]=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])([CH3:3])[CH3:4]

Participants

4

Reactant 3

HCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 516892Sodium BicarbonateHCID 68292455(4-Isopropoxy-3-methyl-phenyl)-[10-(3-methyl-1,2,4-oxadiazol-5-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone hydrochloride salt

Product 1

HCID 66546983HCID 66546983, compoundYield 10.1%

Conditions

Temperature
80 °C

Procedure

A mixture of (4-isopropoxy-3-methyl-phenyl)-[10-(3-methyl-1,2,4-oxadiazol-5-yl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]methanone hydrochloride salt (28 mg, 0.06 mmol), 2,2,2-trifluoroethyl trifluoromethanesulfonate (14 μL, 0.09 mmol) and NaHCO3 (21 mg, 0.23 mmol) 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/H2 0 (5 mM HCl)) and concentrated 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, 10%) as a white solid. ESI-MS m/z calc. 496.5. Found 497.7 (M+1)+; Retention time: 1.99 minutes (3 min run); 1H NMR (400 MHz, DMSO) δ 7.27-7.06 (m, 2H), 6.96 (d, J=9.1 Hz, 1H), 5.17 (dd, J=13.6, 4.2 Hz, 1H), 4.63 (dt, J=12.1, 6.2 Hz, 1H), 3.31-3.19 (m, 5H), 2.92-2.81 (m, 1H), 2.67 (dd, J=12.0, 10.1 Hz, 1H), 2.43-2.27 (m, 6H), 2.15 (s, 3H), 1.70-1.40 (m, 4H), 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/H2 0 (5 mM HCl)) and concentrated

Sources & evidence

ORD record
ord-b62e2ff0aed44ce7991e9b9bc779b0ec
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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