Trifluoroacetic acid → 3-(2-Methoxy-5-nitrobenzyl)-8-(3-phenoxypropyl)-1-oxa-3,8-diazaspiro[4.5]decan-2-one

HRID 1691659Notes

Reaction equation

HRID 1691659 reaction equation
C(OC([N:8]1[CH2:30][CH2:29][C:11]2([O:15][C:14](=[O:16])[N:13]([CH2:17][C:18]3[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[CH:21]=[CH:20][C:19]=3[O:27][CH3:28])[CH2:12]2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.C(N(C(C)C)CC)(C)C.[O:47]([CH2:54][CH2:55][CH2:56]Br)[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>C(Cl)Cl.CCOC(C)=O.O>[CH3:28][O:27][C:19]1[CH:20]=[CH:21][C:22]([N+:24]([O-:26])=[O:25])=[CH:23][C:18]=1[CH2:17][N:13]1[CH2:12][C:11]2([CH2:10][CH2:9][N:8]([CH2:56][CH2:55][CH2:54][O:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[CH2:30][CH2:29]2)[O:15][C:14]1=[O:16]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 68522Benzene, (3-bromopropoxy)-HCID 81531DiisopropylethylamineHCID 576662783-(2-Methoxy-5-nitrobenzyl)-2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylic acid tert-butyl ester

Product 1

HCID 119922233-(2-Methoxy-5-nitrobenzyl)-8-(3-phenoxypropyl)-1-oxa-3,8-diazaspiro[4.5]decan-2-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Compound A8 (0.67 g, 1.59 mmol) was dissolved in DCM (3 mL) and combined with trifluoroacetic acid (3 mL). The reaction mixture was stirred for 5 min at RT and the solvent was then removed under a vacuum. The residue was combined repeatedly with toluene and the solvent was then removed again. The residue was then combined with sat. aq. NaHCO3 solution and repeatedly extracted with EtOAc. The combined organic phases were dried over Na2SO4 and the solvent was removed under a vacuum. The residue was redissolved in anhydrous THF (5 mL) and combined with diisopropylethylamine (333 μL, 1.91 mmol). The reaction mixture was combined with 3-phenoxypropyl bromide (277 μL, 1.75 mmol), stirred for 18 h at RT and combined with water and EtOAc. The organic phase was separated off and the aqueous phase repeatedly extracted with EtOAc. The combined organic phases were dried over Na2SO4 and the solvent was removed under a vacuum. The residue was purified by column chromatography (SiO2, DCM/MeOH 98:2). 433 mg (58% of theoretical) of the desired product 3-(2-methoxy-5-nitrobenzyl)-8-(3-phenoxypropyl)-1-oxa-3,8-diazaspiro[4.5]decan-2-one (432) were obtained.

Workup

  1. customthe solvent was then removed under a vacuum
  2. customthe solvent was then removed again
  3. extractionrepeatedly extracted with EtOAc
  4. dry with materialThe combined organic phases were dried over Na2SO4
  5. customthe solvent was removed under a vacuum
  6. dissolutionThe residue was redissolved in anhydrous THF (5 mL)
  7. stirringstirred for 18 h at RT
  8. customThe organic phase was separated off
  9. extractionthe aqueous phase repeatedly extracted with EtOAc
  10. dry with materialThe combined organic phases were dried over Na2SO4
  11. customthe solvent was removed under a vacuum
  12. customThe residue was purified by column chromatography (SiO2, DCM/MeOH 98:2)

Sources & evidence

ORD record
ord-c4e333a6d9774a5e825a78eafcb4dcc6
Source dataset
uspto-grants-2012_04
Patent number
US08153795B2

Reaction notes

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