Dibromomethane → HCID 86750038, compound

HRID 1902164Notes

Reaction equation

HRID 1902164 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2([C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=CC(OCC)=O)[CH2:14]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])[CH3:3].BrCBr.[CH3:31]C1CCCN(C)C1(C)C.[Li].C[Si](C)(C)N[Si](C)(C)C.[Li].[Li]CCCC.CCO.[CH3:60][CH2:61][O:62][C:63]([CH3:65])=[O:64]>C1COCC1.[Pd]>[CH2:61]([O:62][C:63](=[O:64])[CH2:65][CH2:31][CH:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:11]2([CH2:12][CH2:13][N:8]([C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[CH2:9][CH2:10]2)[CH2:14]1)[CH3:60]

Participants

9

Reactant 6

HCID 3024DibromomethaneHCID 21584252Ethanol ethylacetateHCID 54355242HCID 54355242, compoundHCID 57426343Lithium bis(trimethylsilyl)amideHCID 66701855Lithium tetramethylpiperidineHCID 178418339Butyllithium

Product 1

HCID 86750038HCID 86750038, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A mixture of the title compound (1.0388 g, 2.8 mmol) from Example 98, Step A, and Pd/C (0.28 g) in EtOH/EtOAc (80 ml) was hydrogenated with a balloon for 30 min. The mixture was filtered and the solvent was evaporated. To a solution of the residue and dibromomethane (0.43 ml, 6.16 mmol) in THF (20 ml) at -78° C. for 10 min, was added dropwise a freshly prepared solution of lithium tetramethylpiperidine (6.16 mmol) in THF (10 ml) at 0° C. over 10 min. The mixture was stirred at -78° C. for 10 min. A newly prepared lithium hexamethyldisilazane (5.6 mmol) in THF (10 ml) at 0° C. was added dropwise in 5 min to the mixture at -78° C. The mixture was then slowly warmed to 0° C. in an ice-bath for 30 min. n-BuLi (10.5 ml, 16.8 mmol, 1.6M) was added slowly over 10 min. The mixture was stirred at 0° C. for 5 min and warmed to room temperature for 45 min. The color of the solution changed from yellow to brown. The mixture was then cooled to -78° C. and quenched into a stirred solution of acidic ethanol (30 ml) dropwise at 0° C. over 30 min. The solution was diluted with EtOAc (200 ml) and washed with 1N HCl (30 ml). The aqueous was extracted with EtOAc (2×30 ml). The combined EtOAc layers were washed with brine, and dried over sodium sulfate. The title compound was obtained in 48% yield (0.522 g) as a colorless oil by flash column (EtOAc:hexane=1:9).

Workup

  1. filtrationThe mixture was filtered
  2. customthe solvent was evaporated
  3. additionwas added slowly over 10 min
  4. stirringThe mixture was stirred at 0° C. for 5 min
  5. temperaturewarmed to room temperature for 45 min
  6. temperatureThe mixture was then cooled to -78° C.
  7. customquenched into a stirred solution of acidic ethanol (30 ml) dropwise at 0° C. over 30 min
  8. additionThe solution was diluted with EtOAc (200 ml)
  9. washwashed with 1N HCl (30 ml)
  10. extractionThe aqueous was extracted with EtOAc (2×30 ml)
  11. washThe combined EtOAc layers were washed with brine
  12. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-4e1eb9cea2cb4a0ab00900c0e07b4bfd
Source dataset
uspto-grants-1996_11
Patent number
US05578593

Reaction notes

Loading…