Benzyl Bromide → 1-Benzylspiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]

HRID 1907984Notes

Reaction equation

HRID 1907984 reaction equation
[CH:1]1[N:9]2[C:4]([C:5]3([CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[O:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=32)=[CH:3][CH:2]=1.C([O-])(O)=O.[Na+].[CH2:24](Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C(#N)C>[CH2:24]([N:16]1[CH2:17][CH2:18][C:5]2([O:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=3[N:9]3[CH:1]=[CH:2][CH:3]=[C:4]23)[CH2:14][CH2:15]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 516892Sodium BicarbonateHCID 58550727Spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]

Product 1

HCID 585510631-Benzylspiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]Yield 55.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a 0° C. solution of spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine] (HCl salt) (1.0 g, 3.6 mmol) in dry acetonitrile (10 mL), under nitrogen, was added NaHCO3 (1.5 g, 18 mmol) followed by dropwise addition of benzyl bromide (560 μL, 4.7 mmol). The cooling bath was removed. Water (25 ml) was then added, and the organic solvent was removed under vacuum. The product was extracted from the aqueous solution with EtOAc (3×150 mL). The organic phases were combined, washed with brine, dried with sodium sulfate, filtered, and concentrated under reduced pressure. The product was purified by column chromatography (silica gel: 5-70% EtOAc in hexanes) to give 1′-benzylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine] 660 mg, 55%). ESI-MS m/z calc. 330.4. found 331.5 (M+1)+; Retention time: 1.23 minutes (3 min run).

Workup

  1. customThe cooling bath was removed
  2. additionWater (25 ml) was then added
  3. customthe organic solvent was removed under vacuum
  4. extractionThe product was extracted from the aqueous solution with EtOAc (3×150 mL)
  5. washwashed with brine
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe product was purified by column chromatography (silica gel: 5-70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-b3e1a0b09ee34cb09b3f236557bb7470
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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