Sodium hydride → HCID 59201612, compound

HRID 451719Notes

Reaction equation

HRID 451719 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([C@@:10]([C@@H:15]2[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16]2)([OH:14])[CH2:11][CH2:12][CH3:13])[CH:7]=[CH:8][CH:9]=1.Br[CH2:29][CH2:30][O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33].[NH4+].[Cl-]>C1COCC1>[Si:32]([O:31][CH2:30][CH2:29][O:14][C@:10]([C@@H:15]1[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:16]1)([C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([Cl:3])[CH:5]=1)[CH2:11][CH2:12][CH3:13])([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 68712937HCID 68712937, compound

Product 1

HCID 59201612HCID 59201612, compoundYield 10.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of NaH (2.4 g, 60 mmol) in dry THF (20 mL) was added a solution of (R)-tert-butyl 3-((R)-1-(3-chlorophenyl)-1-hydroxybutyl)piperidine-1-carboxylate (7.34 g, 20 mmol) in dry THF (80 mL) at 0° C. The reaction mixture was stirred at rt for 2 h. Then a solution of (2-bromoethoxy)(tert-butyl)dimethylsilane (14.3 g, 60 mmol) in THF (100 mL) was added dropwise. After addition, the resulting mixture was stirred under reflux overnight. To the reaction mixture was added dropwise saturated NH4Cl solution, extracted by EtOAc (2×100 mL), washed with brine, dried over Na2SO4, and concentrated in vacuo to give the crude product. The crude product was purified by column chromatography on silica gel to afford (R)-tert-butyl 3-((R)-1-(2-(tert-butyldimethylsilyloxy)ethoxy)-1-(3-chlorophenyl)butyl)piperidine-1-carboxylate (1.1 g, 10%). 1H NMR (CDCl3, 400 MHz) δ 7.35 (s, 1H), 7.22 (m, 3H), 4.05 (m, 2H), 3.81 (m, 2H), 3.31 (m, 2H), 2.42 (t, 3H), 2.06 (m, 3H), 1.85 (m, 2H), 1.58 (m, 2H), 1.44 (s, 9H), 1.41-1.01 (m, 7H), 0.92 (s, 9H), 0.095 (s, 6H).

Workup

  1. additionAfter addition
  2. stirringthe resulting mixture was stirred
  3. temperatureunder reflux overnight
  4. extractionextracted by EtOAc (2×100 mL)
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customto give the crude product
  9. customThe crude product was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-10088b7d475c4fc492771cec84a556bb
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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