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

HRID 73037Notes

Reaction equation

Cl.[OH:2][CH2:3][CH2:4][CH:5]1[O:28][C:9]2([CH2:14][CH2:13][N:12]([C:15]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH:24]([CH3:26])[CH3:25])=[C:19]([CH3:27])[CH:18]=3)=[O:16])[CH2:11][CH2:10]2)[CH2:8][NH:7][CH2:6]1.C([O-])(O)=O.[Na+].FC(F)(F)S(O[CH2:40][C:41]([F:44])([F:43])[F:42])(=O)=O>C(O)C>[OH:2][CH2:3][CH2:4][CH:5]1[O:28][C:9]2([CH2:14][CH2:13][N:12]([C:15]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH:24]([CH3:26])[CH3:25])=[C:19]([CH3:27])[CH:18]=3)=[O:16])[CH2:11][CH2:10]2)[CH2:8][N:7]([CH2:40][C:41]([F:44])([F:43])[F:42])[CH2:6]1

Participants

Conditions

Temperature: 80 °C

Procedure

To [10-(2-hydroxyethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone hydrochloride salt (20 mg, 0.05 mmol) and NaHCO3 (16 mg, 0.19 mmol) in ethanol (0.5 mL) was added 2,2,2-trifluoroethyl trifluoromethanesulfonate (11 μL, 0.07 mmol) and the reaction mixture heated in a sealed vial at 80° C. for 5 hours. The reaction mixture was microfiltered and purified by prep LCMS (10-99% ACN/Water, 5 mM HCl modifier) to give [10-(2-hydroxyethyl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (16 mg, 87%) as a colorless oil ESI-MS m/z calc. 458.2. Found 459.7 (M+1)+; Retention time: 1.78 minutes (3 min run).

Workup

custompurified by prep LCMS (10-99% ACN/Water, 5 mM HCl modifier)

Sources & evidence

ORD record: ord-e7e7e736c954483cae00af57e83a6e20
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08828996B2

Reaction notes

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