2,2,2-Trifluoroethyl trifluoromethanesulfonate → [10-(1-Hydroxy-1-methyl-ethyl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone

HRID 73035Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

(2-(2-Hydroxypropan-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)(4-isopropoxy-3-methylphenyl)methanone (25 mg, 0.06 mmol) was dissolved in dry ethanol (300 μL) and NaHCO3 (50 mg, 0.60 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (20 μL, 0.13 mmol) were added and the reaction mixture was heated at 80° C. for 16 hours. The reaction mixture was filtered, concentrated in vacuo and purified by silica gel column chromatography using 0-100% EtOAc/hexanes as eluent to give [10-(1-hydroxy-1-methyl-ethyl)-8-(2,2,2-trifluoroethyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (15 mg, 53%) as a colorless oil. ESI-MS m/z calc. 472.5. Found 473.5 (M+1)+; Retention time: 1.93 minutes (3 min run).

Workup

filtrationThe reaction mixture was filtered
concentrationconcentrated in vacuo
custompurified by silica gel column chromatography

Sources & evidence

ORD record: ord-3e0f4eb2c4b74adbb59892e15bd57aeb
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08828996B2

Reaction notes

Loading…