Ethyl bromoacetate → HCID 59652009, compound

HRID 221827Notes

Reaction equation

HRID 221827 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21]C(=O)C)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[K+].BrCC([O:39][CH2:40][CH3:41])=O.O.[NH2:43][NH2:44].[CH2:45]1[CH2:49]OCC1>CCO>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH:21]3[CH2:41][C:40](=[O:39])[NH:44][N:43]=[C:49]3[CH3:45])=[CH:17][CH:16]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 7748Ethyl bromoacetateHCID 8028TetrahydrofuranHCID 24654Hydrazine hydrate (1:1)HCID 3251421Potassium bis(trimethylsilyl)amideHCID 59651914HCID 59651914, compound

Product 1

HCID 59652009HCID 59652009, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
85 °C

Procedure

A solution of the intermediate from Example 102 step 1 (1.0 g, 3.0 mmol) in THF (10 mL) at −78° C. under N2 was added KHMDS (0.5 M in toluene, 9.0 mL) dropwise. After 30 min at −78° C., ethyl bromoacetate (0.75 g, 4.5 mmol) was added drop wise. After 1 hr at −78° C., the reaction was quenched with 1 N HCl (4.0 mL), diluted with 20 mL of EtOAc and the layers separated. The EtOAc layer was washed with 5% NaHCO3, NaCl solution, then dried over Na2SO4 and concentrated. To the crude solid in 10 mL of EtOH was added hydrazine hydrate (0.22 g, 0.45 mmol) and the reaction then stirred at 85° C. for 2 h. The mixture was cooled to rt, the solvent was reduced and the solid was filtered and washed with cold EtOH to give 0.65 g (56%) of 4-[4-(3-methyl-6-oxo-1,4,5,6-tetrahydro-pyridazin-4-yl)-phenoxyl]-piperidine-1-carboxylic acid tert-butyl ester: Mp 165-7° C.; MS m/z 288 (M-Boc+H).

Workup

  1. waitAfter 1 hr at −78° C.
  2. customthe reaction was quenched with 1 N HCl (4.0 mL)
  3. additiondiluted with 20 mL of EtOAc
  4. customthe layers separated
  5. washThe EtOAc layer was washed with 5% NaHCO3, NaCl solution
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customthe reaction
  9. temperatureThe mixture was cooled to rt
  10. filtrationthe solid was filtered
  11. washwashed with cold EtOH

Sources & evidence

ORD record
ord-84b93db7464747ad98b6cfea6685f5ae
Source dataset
uspto-grants-2012_06
Patent number
US08207168B2

Reaction notes

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