Hydrochloric Acid → 6'-(3-Fluoropropoxy)-1'-imino-1',3'-dihydrospiro[cyclohexane-1,2'-inden]-4-ol

HRID 1467926Notes

Reaction equation

HRID 1467926 reaction equation
[F:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[CH2:11][C:10]1([CH2:19][CH2:18][CH:17]([OH:20])[CH2:16][CH2:15]1)[C:9]2=[N:21]S(C(C)(C)C)=O.Cl>O1CCOCC1>[F:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:12]([CH2:11][C:10]3([CH2:15][CH2:16][CH:17]([OH:20])[CH2:18][CH2:19]3)[C:9]2=[NH:21])=[CH:13][CH:14]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86706683N-(5'-(3-Fluoropropoxy)-4-hydroxyspiro[cyclohexane-1,2'-indene]-3'(1'H)-ylidene)-2-methylpropane-2-sulfinamide2×

Product 1

HCID 867066846'-(3-Fluoropropoxy)-1'-imino-1',3'-dihydrospiro[cyclohexane-1,2'-inden]-4-olYield 111.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To N-(5′-(3-fluoropropoxy)-4-hydroxyspiro[cyclohexane-1,2′-indene]-3′(1′H)-ylidene)-2-methylpropane-2-sulfinamide (Intermediate 32, 275 mg, 0.70 mmol) in dioxane (1 mL) under an atmosphere of nitrogen was added HCl (4 M in 1,4-dioxane, 1.74 mL, 6.95 mmol). The mixture was stirred at r.t. for 2 h and was then concentrated. DCM (1-2 mL) and Et2O was added and a solid was formed. The solid was filtered off and washed with diethylether. The solid was dissolved in DCM. Sat. aq. NaHCO3 was added and mixture was poured in to a phase separator. The organic phase was collected and concentrated to give 6′-(3-fluoropropoxy)-1′-imino-1′,3′-dihydrospiro[cyclohexane-1,2′-inden]-4-ol (227 mg). The obtained imine was mixed with 2-oxopropanethioamide (Intermediate 1, 239 mg, 2.32 mmol) in dry MeOH (4 mL) and the resulting orange solution was heated at 60° C. under an atmosphere of nitrogen overnight. The mixture was allowed to cool to r.t., and concentrated. The residue was purified by flash column chromatography using a gradient of 0-100% EtOAc in heptane, providing 104 mg (36% yield) of the title compound. 1H NMR (500 MHz, DMSO-d6) δ ppm 1.04-1.21 (m, 4 H) 1.41-1.48 (m, 2 H) 1.66-1.73 (m, 2 H) 2.02 (t, 1 H) 2.07 (quin, 1 H) 2.26 (s, 3 H) 2.93 (d, 1 H) 3.01 (d, 1 H) 3.22-3.29 (m, 1 H) 3.97 (tq, 2 H) 4.52 (t, 1 H) 4.55 (d, 1 H) 4.62 (t, 1 H) 6.32 (d, 1 H) 6.89 (dd, 1 H) 7.26 (d, 1 H) 12.28 (s, 1 H); MS (ES+) m/z 377.07 [M+H]+.

Workup

  1. concentrationwas then concentrated
  2. additionDCM (1-2 mL) and Et2O was added
  3. customa solid was formed
  4. filtrationThe solid was filtered off
  5. washwashed with diethylether
  6. dissolutionThe solid was dissolved in DCM
  7. additionSat. aq. NaHCO3 was added
  8. additionmixture was poured in to a phase separator
  9. customThe organic phase was collected
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-6eef86ac363642c6aebb27074037226f
Source dataset
uspto-grants-2015_04
Patent number
US09000182B2

Reaction notes

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