Nitrogen → 2-(methyl(trityl)amino)-1-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-5-yl)ethanol

HRID 23720Notes

Reaction equation

[CH3:1][Si:2]([CH3:13])([CH3:12])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[CH:11]=[CH:10][CH:9]=[N:8]1.[Li]CCCC.N#N.[CH3:21][N:22]([CH2:42][CH:43]=[O:44])[C:23]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1COCC1.CCOCC>[CH3:21][N:22]([C:23]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)([C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:42][CH:43]([C:11]1[N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:13])([CH3:12])[CH3:1])[N:8]=[CH:9][CH:10]=1)[OH:44]

Participants

Conditions

Temperature: -79 °C

Procedure

A solution of 1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazole (Heterocycles (1992), 34(2), 303-14)(0.80 g, 4.03 mmol) in 50 mL of THF/ether (3/2) was cooled to −78° C. and treated with 2.5M solution of n-BuLi (1.8 mL, 4.43 mmol) dropwise under N2 atmosphere. The resulting mixture was stirred for 30 min. [Methyl(trityl)amino]acetaldehyde (1.27 g, 4.04 mmol) in 5 mL of the THF/ether solution was added to reaction mixture and stirred for 1 h at −79° C. and warmed up to room temperature. The reaction was quenched by adding NH4Cl (sat. aq.) and water dropwise and the resulting suspension was extrcted into EtOAc (2×100 mL). The organic phase was washed with water (100 mL) and brine (50 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was chromatographed on a Flash 40M silica gel (90 g, 32-63 μm) cartridge, eluting with 20% EtOAc in n-heptane, and those fractions with Rf=0.3 by TLC(EtOAc/hexane, 3/7) were combined and concentrated in vacuo to give 0.7 g of the product as a white solid.

Workup

additionwas added to reaction mixture
temperaturewarmed up to room temperature
customThe reaction was quenched
additionby adding NH4Cl (sat. aq.) and water dropwise
washThe organic phase was washed with water (100 mL) and brine (50 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was chromatographed on a Flash 40M silica gel (90 g, 32-63 μm) cartridge
washeluting with 20% EtOAc in n-heptane
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-8be54bab72464c909ed53c8be98da4a2
Source dataset: uspto-grants-2005_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06852731B2

Reaction notes

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