Trifluoroacetic acid → Ethyl 2-(4-bromo-2-fluorophenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetate

HRID 1525921Notes

Reaction equation

HRID 1525921 reaction equation
[CH2:1]([N:3]1[CH2:8][C:7]2([CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]2)[O:6][CH2:5][C:4]1=[O:21])[CH3:2].C(O)(C(F)(F)[F:25])=O.C(=O)([O-])[O-].[K+].[K+].Br[CH:36]([C:42]1[CH:47]=[CH:46][C:45]([Br:48])=[CH:44][CH:43]=1)[C:37]([O:39][CH2:40][CH3:41])=[O:38]>ClCCl.O>[Br:48][C:45]1[CH:46]=[CH:47][C:42]([CH:36]([N:11]2[CH2:12][CH2:13][C:7]3([O:6][CH2:5][C:4](=[O:21])[N:3]([CH2:1][CH3:2])[CH2:8]3)[CH2:9][CH2:10]2)[C:37]([O:39][CH2:40][CH3:41])=[O:38])=[C:43]([F:25])[CH:44]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 12754876Ethyl 2-bromo-(4-bromophenyl)acetateHCID 71270774Tert-butyl 4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

Product 1

HCID 71270877Ethyl 2-(4-bromo-2-fluorophenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate (1 g, 3.35 mmol) in dichloromethane (10 mL) was added TFA (0.775 mL, 10.05 mmol). The reaction mixture was stirred at room temperature overnight, at which point the deprotection had proceeded to completion. The reaction mixture was concentrated in vacuo, dichloromethane was added, and the solution was concentrated in vacuo again. The residue was dissolved with N,N-dimethylformamide (12 mL). To this solution was added potassium carbonate (0.463 g, 3.35 mmol) and ethyl 2-bromo-2-(4-bromophenyl)acetate (1.079 g, 3.35 mmol). The reaction mixture was stirred at 40° C. for overnight, at which point the reaction had proceeded to completion. The reaction mixture was poured into water (120 mL) and was extracted with ethyl acetate (80 mL×3). The combined organic layers were dried and concentrated in vacuo. Crude ethyl 2-(4-bromo-2-fluorophenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetate was obtained (590 mg) and was used directly in the next step. MS(ES)+ m/e 457 [M+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo, dichloromethane
  2. additionwas added
  3. concentrationthe solution was concentrated in vacuo again
  4. dissolutionThe residue was dissolved with N,N-dimethylformamide (12 mL)
  5. stirringThe reaction mixture was stirred at 40° C. for overnight, at which
  6. extractionwas extracted with ethyl acetate (80 mL×3)
  7. customThe combined organic layers were dried
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-71e0fda66ae04575bfc195f9d1444ff1
Source dataset
uspto-grants-2015_07
Patent number
US09084794B2

Reaction notes

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