Ethyl bromoacetate → HCID 66864899, compound

HRID 1615834Notes

Reaction equation

HRID 1615834 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH3:28])[NH:14][C:13](=[O:15])[C:12]3([CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)[N:11]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[H-].[Na+].Br[CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34].C([O-])(O)=O.[Na+]>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH3:28])[N:14]([CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[C:13](=[O:15])[C:12]3([CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]3)[N:11]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 66865101HCID 66865101, compound

Product 1

HCID 66864899HCID 66864899, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of tert-butyl (3R)-3-(3,5-difluorophenyl)-3-methyl-5-oxo-1,4-diazaspiro[5.5]undecane-1-carboxylate from Step H (60 mg, 0.152 mmol) in THF (0.5 mL) at 0° C. was added NaH (12 mg of a 60% dispersion in oil, 0.30 mmol). After 5 min, ethyl bromoacetate (437 mg, 2.62 mmol) was added and the mixture was allowed to warm to ambient temperature and stirring was continued for 1 h. Saturated aqueous NaHCO3 (2 mL) was added and the mixture was extracted with EtOAc (2×5 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—95:5 to 60:40, to give the title compound. MS: m/z=425 (M−C4H7).

Workup

  1. waitwas continued for 1 h
  2. extractionthe mixture was extracted with EtOAc (2×5 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by silica gel chromatography
  7. washeluting with a gradient of hexane

Sources & evidence

ORD record
ord-b2900515dc6b445185b4aec8c5930a0c
Source dataset
uspto-grants-2014_07
Patent number
US08765759B2

Reaction notes

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