Sodium hydride → HCID 16731688, compound

HRID 456432Notes

Reaction equation

HRID 456432 reaction equation
[H-].[Na+].[C:3]([N:10]1[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]1)([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[Br:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1F>CN(C=O)C.CCOC(C)=O>[C:3]([N:10]1[CH2:15][CH2:14][CH:13]([O:16][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[Br:17])[CH2:12][CH2:11]1)([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 612591-Bromo-2-fluorobenzeneHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 16731688HCID 16731688, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a slurry of NaH (60% dispersion in oil, 5.9 g, 148.5 mmol, 3.0 eq.) in DMP (40 mL) at 65° C. under N2 was added a solution of N-boc-4-hydroxy piperidine (10 g, 49.5 mmol, 1.0 eq.) in DMF (50 mL). After stirring for about 2 hours, a solution of 1-bromo-2-fluoro benzene (11.0 mL, 99.0 mmol, 2.0 eq.) in DMF (10 mL) was added dropwise. The resulting mixture was stirred at 65° C. overnight. The mixture was diluted with EtOAc (250 mL) and washed with water (100 mL) and brine (100 mL). The aqueous layer was extracted with EtOAc (3×). The combined organic extracts were dried (Na2SO4), filtered and concentrated. Purification by flash chromatography (250 g SiO2, linear gradient, 40 mL/min, 0% to 30% EtOAc/Hexane over 20 minutes and 30% EtOAc for 13 minutes) afforded title compound (14.2 g, 39.8 mmol, 81%). LRMS (electrospray): 358.0.

Workup

  1. stirringThe resulting mixture was stirred at 65° C. overnight
  2. washwashed with water (100 mL) and brine (100 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (3×)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash chromatography (250 g SiO2, linear gradient, 40 mL/min, 0% to 30% EtOAc/Hexane over 20 minutes and 30% EtOAc for 13 minutes)

Sources & evidence

ORD record
ord-f979201bb5c24a9f902514b38b09e26f
Source dataset
uspto-grants-2007_03
Patent number
US07186715B2

Reaction notes

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