Methyl iodide → HCID 86685701, compound

HRID 1053998Notes

Reaction equation

HRID 1053998 reaction equation
[CH2:1]([O:3][C:4](=[O:29])[CH:5]([CH3:28])[CH2:6][C:7]1[CH:11]=[C:10]([CH3:12])[N:9]([CH2:13][C:14]2[CH:19]=[C:18]([Br:20])[CH:17]=[CH:16][C:15]=2[O:21][CH2:22][CH:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)[N:8]=1)[CH3:2].[CH3:30]I>C1COCC1>[CH2:1]([O:3][C:4](=[O:29])[C:5]([CH3:30])([CH3:28])[CH2:6][C:7]1[CH:11]=[C:10]([CH3:12])[N:9]([CH2:13][C:14]2[CH:19]=[C:18]([Br:20])[CH:17]=[CH:16][C:15]=2[O:21][CH2:22][CH:23]2[CH2:24][CH2:25][CH2:26][CH2:27]2)[N:8]=1)[CH3:2]

Participants

4

Reactant 2

HCID 6328Methyl iodideHCID 86685702HCID 86685702, compound

Product 1

HCID 86685701HCID 86685701, compoundYield 38.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-{1-[5-bromo-2-(2-cyclopentylmethoxy)-benzyl]-5-methyl-1H-pyrazol-3-yl}-2-methyl-propionic acid ethyl ester (0.14 g, 0.3 mmol) in dry THF (5 ml) under a N2 atmosphere at −78° C. was added lithium bis(trimethylsislyl)amide (1.8 ml, 1M in THF). The mixture was stirred for 1 hour before addition of a THF solution (1 ml) of MeI (0.255 g, 0.18 mmol). After stirring 3 hours more at −78° C. the mixture was left at RT for 16 hours. The reaction was quenched with sat NH4Cl solution and extracted with EtOAc. The organic layer was washed with brine, dried (MgSO4) and evaporated to dryness. The residue was purified by MPLC (10 g SiO2 cartridge, eluent 95-90% iso-hexane-5-10% EtOAc) to yield 0.033 g of 3-{1-[5-bromo-2-(2-cyclopentylmethoxy)-benzyl]-5-methyl-1H-pyrazol-3-yl}-2,2-dimethyl-propionic acid ethyl ester which was converted to the title compound following the method in Example 1, Step 8.

Workup

  1. waitwas left at RT for 16 hours
  2. customThe reaction was quenched with sat NH4Cl solution
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated to dryness
  7. customThe residue was purified by MPLC (10 g SiO2 cartridge, eluent 95-90% iso-hexane-5-10% EtOAc)

Sources & evidence

ORD record
ord-f5e03d1a817e46de996b10c90a746244
Source dataset
uspto-grants-2016_07
Patent number
US09394284B2

Reaction notes

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