Pyrrolidine → (+/-)-6-bromo-3,4-dihydro-4-oxo-spiro-[2H-(1,3)-benzoxazine-2,3'-piperidine]-1'-carboxylic acid tert-butyl ester

HRID 874225Notes

Reaction equation

HRID 874225 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH2:11][C:10](=[O:14])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[Br:15][C:16]1[CH:17]=[CH:18][C:19](O)=[C:20]([CH:24]=1)[C:21]([NH2:23])=[O:22].N1CCCC1>CO>[C:4]([O:3][C:1]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]2([NH:23][C:21](=[O:22])[C:20]3[CH:24]=[C:16]([Br:15])[CH:17]=[CH:18][C:19]=3[O:14]2)[CH2:9]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 728765-BromosalicylamideHCID 2756825Tert-butyl 3-oxopiperidine-1-carboxylate

Product 1

HCID 67071706(+/-)-6-bromo-3,4-dihydro-4-oxo-spiro-[2H-(1,3)-benzoxazine-2,3'-piperidine]-1'-carboxylic acid tert-butyl esterYield 68.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

1-BOC-piperidin-3-one (4.0 g, 20 mmol) was added to a mixture of 5-bromo-2-hydroxybenzamide (2.0 g, 9.2 mmol) and pyrrolidine (0.76 ml, 9.2 mmol) in MeOH (7.5 ml), and the reaction mixture was heated to 70° C. by MW (closed vessel) for 5 h. The solution was then concentrated under vacuum and the crude mixture was purified by column chromatography on silica gel (eluent: DCM/EtOAc 7:3) to give (±)-6-bromo-3,4-dihydro-4-oxo-spiro-[2H-(1,3)-benzoxazine-2,3′-piperidine]-1′-carboxylic acid tert-butyl ester (2.50 g) as a yellow solid.

Workup

  1. concentrationThe solution was then concentrated under vacuum
  2. customthe crude mixture was purified by column chromatography on silica gel (eluent: DCM/EtOAc 7:3)

Sources & evidence

ORD record
ord-8a5fdcabdfc7405688f78f87d07449c8
Source dataset
uspto-grants-2015_03
Patent number
US08980877B2

Reaction notes

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