PEG4-tert-butyl acetate Chemical Properties

Boiling point:

393.1±32.0 °C(Predicted)

Density 

1.077±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

Soluble in Water, DMSO, DCM, DMF

pka

14.36±0.10(Predicted)

form 

Liquid

color 

Colorless to light yellow

PEG4-tert-butyl acetate Usage And Synthesis

Description

Hydroxy-PEG4-CH2CO2tBu is a PEG linker containing a hydroxyl group with a t-butyl protected carboxyl group. The hydrophilic PEG spacer increases solubility in aqueous media. The hydroxyl group enables further derivatization or replacement with other reactive functional groups. The t-butyl protected carboxyl group can be deprotected under acidic conditions.

Uses

Hydroxy-PEG4-CH2-Boc is a PEG-based PROTAC linker can be used in the synthesis of PROTACs.

Synthesis

GENERAL STEPS: To a stirred mixture of tert-butyl 2-bromoacetate (5.4 mL, 36.6 mmol) and 2,2'-((oxo-bis(ethane-2,1-diyl))bis(oxy))diethanol (35.0 mL, 203 mmol) in DMSO (50 mL) was added in two additions of NaH (1.6217 g, 40.6 mmol, a 60% oil solution). The reaction mixture was slowly warmed to room temperature with continuous stirring for 23 hours. Subsequently, the reaction solution was diluted with water (50 mL), saturated with NaCl (50 g), stirred for 5 min and extracted with ether (3 x 100 mL). The organic phases were combined and concentrated. The residue was dissolved in dichloromethane (50 mL) and water (25 mL) and stirred for 5 minutes. The organic phases were separated by a phase separator, concentrated, and purified using an 80 g silica gel column with a gradient of ethyl acetate in hexanes as eluent (50-100%) to afford tert-butyl 14-hydroxy-3,6,9,12-tetraoxatetradecane-1-carboxylate (8.2 g, 72.7% yield) as a light yellow oil. rf = 0.08 (ethyl acetate). NMR hydrogen spectrum (400 MHz, CDCl3) δ 4.02 (d, J = 1.0 Hz, 2H), 3.75-3.60 (m, 12H), 1.47 (s, 9H) ppm. low-resolution mass spectrometry (ESI) m/z: C14H28O7 Calculated value: 308.3679; Measured value: 330.95 (M + Na)+; Measured value: 347.01 (M + K)+.

References

[1] Patent: WO2018/200981, 2018, A1. Location in patent: Paragraph 0209; 0294-0295
[2] Journal of Medicinal Chemistry, 2018, vol. 61, # 2, p. 583 - 598
[3] Patent: US2018/177750, 2018, A1. Location in patent: Paragraph 1106

PEG4-tert-butyl acetate(169751-72-8)Related Product Information

• Hydroxy-PEG5-t-butyl acetate
• Hydroxy-PEG1-CH2CO2tBu
• Hydroxy-PEG2-CH2CO2t-Bu
• Hydroxy-PEG3-t-butyl acetate
• Hydroxy-PEG6-CH2CO2tBu
• Hydroxy-PEG2-CH2CO2H
• CESIUM ACETATE
• Potassium Acetate
• Ammonium acetate
• Zinc acetate
• Cupric acetate monohydrate
• YTTERBIUM(III) ACETATE HYDRATE
• Hydrazine acetate
• TERBIUM(III) ACETATE HYDRATE
• Neodymium(III) acetate hydrate
• YTTRIUM ACETATE
• Sodium acetate trihydrate
• Zinc acetate dihydrate