Ethyl bromoacetate → HCID 59201428, compound

HRID 451685Notes

Reaction equation

HRID 451685 reaction equation
[H-].[Na+].[F:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[CH:11]([OH:25])[C@@H:12]1[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]1.Br[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29].[NH4+].[Cl-]>C1COCC1>[F:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[CH:11]([O:25][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[C@@H:12]1[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:13]1

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 59201677HCID 59201677, compound

Product 1

HCID 59201428HCID 59201428, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of NaH (3.5 g, 88.4 mmol) in THF (100 mL) at 0-5° C. was added dropwise a solution of (R)-tert-butyl 3-((2,3-difluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (9.6 g, 29.5 mmol) in THF (50 mL), the reaction mixture was stirred for 1 h at rt. A solution of ethyl bromoacetate (14.7 g, 88.4 mmol) in THF (50 mL) was added dropwise to the above mixture, and then refluxed for 3-5 h. The reaction mixture was poured into saturated aqueous NH4Cl, then extracted with ethyl acetate, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified on silica gel chromatography to afford (3R)-tert-butyl 3-((2,3-difluorophenyl)(2-ethoxy-2-oxoethoxy)methyl)piperidine-1-carboxylate (9.5 g, 79%). 1H NMR (CDCl3, 400 MHz) δ 7.22 (m, 1H), 7.08 (m, 2H), 4.62 (d, 2H), 4.33 (d, 2H), 4.18 (q, 3H), 3.95 (m, 4H), 3.82 (d, 2H), 2.77 (m, 4H), 1.88 (m, 3H), 1.44 (s, 9H), 1.26 (t, 3H).

Workup

  1. temperaturerefluxed for 3-5 h
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified on silica gel chromatography

Sources & evidence

ORD record
ord-5a1dbbc88ac34dfbbca4ea20914d2a32
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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