Trifluoroacetic acid → Tert-butyl 8-(2,2-difluoropropyl)-10-(methoxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

HRID 713004Notes

Reaction equation

[CH3:1][O:2][CH2:3][CH:4]1[CH2:9][N:8](CC(=O)C)[CH2:7][C:6]2([CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[O:5]1.[CH2:26](N(S(F)(F)F)CC)C.[F-].[Cs+].F[C:38]([F:43])([F:42])[C:39](O)=O>ClCCl>[F:42][C:38]([F:43])([CH3:26])[CH2:39][N:8]1[CH2:9][CH:4]([CH2:3][O:2][CH3:1])[O:5][C:6]2([CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:17][CH2:18]2)[CH2:7]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of tert-butyl 2-(methoxymethyl)-4-(2-oxopropyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate in dichloromethane (1 mL) was added and N,N-diethylaminosulfur trifluoride (195 μL, 1.47 mmol). Cesium fluoride (9.0 mg, 0.059 mmol) was then added in two portions followed by trifluoroacetic acid (5 μL, 0.06 mmol). The reaction was stirred for 15 min then cooled to 0° C. and quenched with 5 mL of saturated aqueous NaHCO3. The reaction was diluted with dichloromethane (5 mL) and the layers separated. The organic layer was washed with water, dried over Na2SO4, filtered and concentrated in vacuo to provide tert-butyl 8-(2,2-difluoropropyl)-10-(methoxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate as yellow oil. ESI-MS m/z calc. 378.2. found 379.3 (M+1)+; Retention time: 1.53 minutes (3 min run).

Workup

customquenched with 5 mL of saturated aqueous NaHCO3
additionThe reaction was diluted with dichloromethane (5 mL)
customthe layers separated
washThe organic layer was washed with water
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-010dba94624e462b8d38e4edb5c05c00
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181273B2

Reaction notes

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