Ethyl bromoacetate → HCID 59598458, compound

HRID 2266248Notes

Reaction equation

HRID 2266248 reaction equation
[H-].[Na+].[F:3][C:4]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[CH:11]=2)=[C:8]([CH:17]([OH:31])[C@@H:18]2[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19]2)[CH:7]=[CH:6][CH:5]=1.Br[CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35].[NH4+].[Cl-]>C1COCC1>[CH2:37]([O:36][C:34](=[O:35])[CH2:33][O:31][CH:17]([C:8]1[CH:7]=[CH:6][CH:5]=[C:4]([F:3])[C:9]=1[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[CH:11]=1)[C@@H:18]1[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:25])[CH2:19]1)[CH3:38]

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 59598495HCID 59598495, compound

Product 1

HCID 59598458HCID 59598458, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of NaH (0.42 g, 17.6 mmol) in THF (50 mL) at 0˜5° C. was added dropwise a solution of (3R)-tert-butyl 3-((6-fluoro-3′-methylbiphenyl-2-yl)(hydroxy)methyl)piperidine-1-carboxylate (3.5 g, 8.8 mmol) in THF (30 mL) and the reaction mixture was stirred for 1 h at rt. A solution of ethyl bromoacetate (2.92 g, 17.6 mmol) in THF (30 mL) was added dropwise to the above mixture, and then refluxed for 12 h. Tlc showed the starting material had disappeared. The reaction mixture was poured into satd aq NH4Cl and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography to afford (3R)-tert-butyl 3-((2-ethoxy-2-oxoethoxy)(6-fluoro-3′-methylbiphenyl-2-yl)methyl)piperidine-1-carboxylate (1.1 g, 38%). 1H NMR (400 MHz, CDCl3): 1.26 (m, 3H), 1.40 (s, 9H), 2.10 (m, 1H), 2.39 (s, 3H), 2.51 (m, 1H), 3.51 (m, 1H), 3.78 (m, 1H), 3.96 (m, 2H), 4.16 (m, 3H), 4.23 (m, 2H), 4.69 (m, 2H), 6.97 (m, 2H), 7.06 (m, 1H), 7.20 (m, 1H), 7.29-7.41 (m, 3H).

Workup

  1. temperaturerefluxed for 12 h
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-71b0580b45bd4189bab8033beddbc510
Source dataset
uspto-grants-2010_12
Patent number
US07858624B2

Reaction notes

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