Hydrochloric Acid → 6'-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-imine

HRID 1468075Notes

Reaction equation

HRID 1468075 reaction equation
Cl.[F:2][C:3]1([F:32])[CH2:6][CH:5]([CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[CH2:14][C:13]2([CH2:22][CH2:21][CH:20]([O:23][CH3:24])[CH2:19][CH2:18]2)[C:12]3=[N:25]S(C(C)(C)C)=O)[CH2:4]1>O1CCOCC1.C([O-])(O)=O.[Na+]>[F:2][C:3]1([F:32])[CH2:6][CH:5]([CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:15]([CH2:14][C:13]4([CH2:22][CH2:21][CH:20]([O:23][CH3:24])[CH2:19][CH2:18]4)[C:12]3=[NH:25])=[CH:16][CH:17]=2)[CH2:4]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86706722N-(5'-((3,3-Difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2'-indene]-3'(1'H)-ylidene)-2-methylpropane-2-sulfinamide2×

Product 1

HCID 867067236'-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-imineYield 116.4%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

HCl (4 M in 1,4-dioxane, 4.13 mL, 16.5 mmol) was added to a solution of N-(5′-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2′-indene]-3′(1′H)-ylidene)-2-methylpropane-2-sulfinamide (Intermediate 18, 750 mg, 1.65 mmol) in anhydrous 1,4-dioxane (25 mL). A white precipitate formed immediately and the resulting cloudy mixture was stirred under a nitrogen atmosphere overnight. The mixture was diluted with NaHCO3 (aq.) and extracted with DCM. The organic phase was dried and concentrated, to yield 6′-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2′-inden]-1′(3′H)-imine (672 mg, 1.92 mmol). The imine, trimethyl orthoformate (0.557 mL, 5.08 mmol) and 2-propanol (5 mL) was placed into a MW tube and the mixture was heated at 60° C. in an oil bath. 2-oxopropanethioamide (Intermediate 1, 397 mg, 3.85 mmol) in MeOH (15 mL) was added and the resulting mixture was stirred overnight. The mixture was concentrated in vacuo. The product was isolated using column chromatography (0-50% EtOAc in heptane) to give 106 mg (12% yield) of the title compound. MS (ES+) m/z 435 [M+H]+.

Workup

  1. customA white precipitate formed immediately
  2. extractionextracted with DCM
  3. customThe organic phase was dried
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-55b30e1edd3d48d58326e4253076e6de
Source dataset
uspto-grants-2015_04
Patent number
US09000185B2

Reaction notes

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