Methanol → 2-(4-Bromo-2-methyl-phenyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester

HRID 1911075Notes

Reaction equation

HRID 1911075 reaction equation
C(O[C:4]([C:6]1([CH2:19][CH2:20][NH:21][C:22]2[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][C:23]=2[CH3:29])[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)=[O:5])C.CC(C)([O-])C.[K+].O.CO>C1COCC1.C(Cl)Cl>[C:15]([O:14][C:12]([N:9]1[CH2:10][CH2:11][C:6]2([C:4](=[O:5])[N:21]([C:22]3[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][C:23]=3[CH3:29])[CH2:20][CH2:19]2)[CH2:7][CH2:8]1)=[O:13])([CH3:18])([CH3:17])[CH3:16]

Participants

7

Reactant 4

HCID 887MethanolHCID 962WaterHCID 23665647Potassium tert-butoxideHCID 674216984-[2-(4-Bromo-2-methyl-phenylamino)-ethyl]-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester

Product 1

HCID 584784512-(4-Bromo-2-methyl-phenyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl esterYield 63%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a clear solution of 4-[2-(4-Bromo-2-methyl-phenylamino)-ethyl]-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (3.42 mmol) in THF (40 mL) was added a solution of potassium t-butoxide (1M in THF) 1 mL (1 mmol, 0.3 equiv.) at r.t. (water bath at rt). The clear solution turned a little bit cloudy. After 30 min, TLC (5% MeOH in DCM) showed the reaction is complete (spot to spot), LC/MS detected the product peak of 423/425 (t 3.267 min). The reaction was cooled in an ice-water bath, diluted with 100 mL of DCM, quenched with 20 mL of water. The two layers were separated. The aqueous layer was extracted with DCM (2×20 mL). The combined DCM extracts were washed with brine, and concentrated on rotavap to yield 0.90 g (63% yield) of the title compound as a white solid.

Workup

  1. customthe product peak of 423/425 (t 3.267 min)
  2. temperatureThe reaction was cooled in an ice-water bath
  3. customquenched with 20 mL of water
  4. customThe two layers were separated
  5. extractionThe aqueous layer was extracted with DCM (2×20 mL)
  6. washThe combined DCM extracts were washed with brine
  7. concentrationconcentrated on rotavap

Sources & evidence

ORD record
ord-2f7f10cc18f24dc1baa25fee8c2b2c3e
Source dataset
uspto-grants-2013_12
Patent number
US08604046B2

Reaction notes

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