Ammonium Chloride → HCID 22473218, compound

HRID 2183512Notes

Reaction equation

HRID 2183512 reaction equation
[Li]CCCC.Br[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][O:14][Si](C(C)(C)C)(C)C)=[CH:9][N:8]=1.[C:22]([N:29]1[CH2:34][CH2:33][C:32](=[O:35])[CH2:31][CH2:30]1)([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23].[NH4+].[Cl-].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[SiH3]O[SiH3]>C1COCC1>[OH:35][C:32]1([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][OH:14])=[CH:9][N:8]=2)[CH2:31][CH2:30][N:29]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:34][CH2:33]1

Participants

8

Reactant 6

HCID 25517Ammonium Chloride2×HCID 123318DisiloxaneHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 2724141Tetrabutylammonium FluorideHCID 6425754Pyridine, 2-bromo-5-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-HCID 178418339Butyllithium

Product 1

HCID 22473218HCID 22473218, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
-78 °C

Procedure

A solution of BuLi (9.94 mmol) in hexanes (1.6 M, 6.2 ml) was added dropwise over 3 min to a stirred solution of 2-bromo-5-(tert-butyldimethylsilyloxymethyl)pyridine (2.0 g, 6.63 mmol) in THF (40 ml) at −78° C. under N2. The resulting solution was then stirred at −78° C. for 30 min and a solution of N-Boc-4-piperidone (1.95 g, 9.93 mmol) in THF (20 ml) was added. The reaction was allowed to warm to room temperature and stirred for a further 15 min. NH4Cl solution (40 ml) was added and the organics were extracted with EtOAc (3×50 ml). The combined organics were washed with brine (50 ml) and then concentrated under reduced pressure. A solution of tetrabutylammonium fluoride(6.63 mmol) in THF (1.0 M, 6.63 ml) was added to a stirred solution of the crude silyl ether in THF (100 ml) at room temperature under N2 and the reaction mixture was stirred for 1 h. NH4Cl solution (40 ml) was added and the organic were extracted with EtOAc (3×50 ml), then washed with brine (50 ml), dried and concentrated under reduced. The mixture was purified by column chromatography on silica using 100% EtOAc as eluent to yield the desired hydroxymethylpyridine (0.89 g, 44%). 1H NMR (360 MHz, CDCl3) δ 8.48 (1H, s), 7.74 (1H, d, J=8.1 Hz), 7.32 (1H, d, J=8.1 Hz), 4.72 (1H, broad s), 4.10 (2H, s), 4.10-4.00 (2H, m), 3.30-3.20 92H, m), 1.89 (2H, td, J=8.1, 4.9 Hz), 1.56 92H, d, J=8.1 Hz), 1.47 (9H, s). m/z (ES+) 423 (M+H+).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for a further 15 min
  3. extractionthe organics were extracted with EtOAc (3×50 ml)
  4. washThe combined organics were washed with brine (50 ml)
  5. concentrationconcentrated under reduced pressure
  6. stirringthe reaction mixture was stirred for 1 h
  7. extractionthe organic were extracted with EtOAc (3×50 ml)
  8. washwashed with brine (50 ml)
  9. customdried
  10. concentrationconcentrated
  11. customThe mixture was purified by column chromatography on silica using 100% EtOAc as eluent

Sources & evidence

ORD record
ord-c99ff4e84f254fecb43fe092b3f016cb
Source dataset
uspto-grants-2005_05
Patent number
US06900209B2

Reaction notes

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