Trifluoroacetic acid → Tert-butyl 2'-methylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]-1'-carboxylate

HRID 1907993Notes

Reaction equation

HRID 1907993 reaction equation
FC(F)(F)C(O)=O.[N:8]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[OH:19])[CH:12]=[CH:11][CH:10]=[CH:9]1.[CH3:20][CH:21]1[CH2:26][C:25](=O)[CH2:24][CH2:23][N:22]1[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29]>ClCCl>[CH3:20][CH:21]1[CH2:26][C:25]2([O:19][C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[N:8]3[CH:9]=[CH:10][CH:11]=[C:12]23)[CH2:24][CH2:23][N:22]1[C:28]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7123342-(1H-Pyrrol-1-Yl)PhenolHCID 12992764tert-Butyl 2-methyl-4-oxopiperidine-1-carboxylate

Product 1

HCID 67468689Tert-butyl 2'-methylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]-1'-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (443 μL, 5.75 mmol) was added to a solution of 2-pyrrol-1-ylphenol (457 mg, 2.87 mmol) and tert-butyl 2-methyl-4-oxo-piperidine-1-carboxylate (613 mg, 2.87 mmol) in dichloromethane (19 mL) and the solution was vigorously stirred for 16 h. The reaction mixture was quenched with saturated aqueous NaHCO3, and the organics were extracted with EtOAc (3×200 mL). The combined organics were washed with water, brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (silica gel: 0-10% EtOAc in dichloromethane) to give tert-butyl 2′-methylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1′-carboxylate as a brown oil. The crude residue was dissolved in a solution of HCl in dioxane (1.4 mL of 4.0 M, 5.6 mmol) and stirred for 30 min at room temperature. The volatiles were removed in vacuo and the residue was dissolved in diethylether. The solids were collected by filtration to provide 2′-methylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]hydrochloride (386 mg, 46%) as a reddish brown solid. ESI-MS m/z calc. 254.1. found 255.5 (M+1)+; Retention time: 1.12 minutes (3 min run).

Workup

  1. customThe reaction mixture was quenched with saturated aqueous NaHCO3
  2. extractionthe organics were extracted with EtOAc (3×200 mL)
  3. washThe combined organics were washed with water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (silica gel: 0-10% EtOAc in dichloromethane)

Sources & evidence

ORD record
ord-146ca86e9dc84c298e8146507c34a5b2
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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