Hydrochloric Acid → 4-(2,2-Difluoroethyl)-2-(oxazol-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane hydrochloride salt

HRID 712963Notes

Reaction equation

HRID 712963 reaction equation
[ClH:1].[F:2][CH:3]([F:28])[CH2:4][N:5]1[CH2:10][C:9]2([CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][CH2:11]2)[O:8][CH:7]([C:23]2[O:24][CH:25]=[CH:26][N:27]=2)[CH2:6]1>C(Cl)Cl>[ClH:1].[F:28][CH:3]([F:2])[CH2:4][N:5]1[CH2:10][C:9]2([CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[O:8][CH:7]([C:23]2[O:24][CH:25]=[CH:26][N:27]=2)[CH2:6]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86672466Tert-butyl 4-(2,2-difluoroethyl)-2-(oxazol-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

Product 1

HCID 866724644-(2,2-Difluoroethyl)-2-(oxazol-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane hydrochloride saltYield 94.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

HCl (781 μL of 4 M in dioxane, 3.12 mmol) was added to a solution of tert-butyl 4-(2,2-difluoroethyl)-2-(oxazol-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate (121 mg, 0.31 mmol) in DCM (0.7 mL) and the reaction mixture was stirred for 1 hour at room temperature. The solvent and excess HCl was removed under reduced pressure and the resulting solid was dissolved in methanol (3 mL) and purified by Waters mass directed LC/MS: (1-99% ACN/H2O (5 mM HCl)). The desired fractions were combined and concentrated in vacuo to yield 4-(2,2-difluoroethyl)-2-(oxazol-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane hydrochloride salt (95 mg, 94%) as a white solid. ESI-MS m/z calc. 287.1. found 288.3 (M+1)+; Retention time: 0.96 minutes (3 min run); 1H NMR (400 MHz, DMSO) δ 8.15 (d, J=0.8 Hz, 1H), 7.23 (d, J=0.8 Hz, 1H), 6.22 (tt, J=55.1, 4.0 Hz, 1H), 4.94 (dd, J=10.8, 2.6 Hz, 1H), 3.19-2.79 (m, 8H), 2.65-2.54 (m, 2H), 2.25 (dd, J=11.9, 1.5 Hz, 1H), 1.83-1.70 (m, 2H), 1.65 (dd, J=15.1, 3.9 Hz, 1H).

Workup

  1. customThe solvent and excess HCl was removed under reduced pressure
  2. dissolutionthe resulting solid was dissolved in methanol (3 mL)
  3. custompurified by Waters mass
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8787af38e0ae422b8837438d48474828
Source dataset
uspto-grants-2015_11
Patent number
US09181273B2

Reaction notes

Loading…