4-BENZYLOXYBUTYRIC ACID

4-BENZYLOXYBUTYRIC ACID Property

Boiling point:

135 °C/0.3 mmHg (lit.)

Density 

1.097 g/mL at 25 °C (lit.)

refractive index 

n20/D 1.512(lit.)

Flash point:

>230 °F

storage temp. 

Sealed in dry,Room Temperature

solubility 

Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly)

pka

4.63±0.10(Predicted)

form 

Oil

color 

Colourless to Pale Yellow

InChI

InChI=1S/C11H14O3/c12-11(13)7-4-8-14-9-10-5-2-1-3-6-10/h1-3,5-6H,4,7-9H2,(H,12,13)

InChIKey

CXEFZVVLTJQWBF-UHFFFAOYSA-N

SMILES

C(O)(=O)CCCOCC1=CC=CC=C1

Safety

Hazard Codes 

C

Risk Statements 

34

Safety Statements 

26-27-36/37/39-45

RIDADR 

UN 3265 8/PG 2

WGK Germany 

3

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H314Causes severe skin burns and eye damage

Precautionary statements

P280Wear protective gloves/protective clothing/eye protection/face protection.

P303+P361+P353IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P363Wash contaminated clothing before reuse.

P405Store locked up.

4-BENZYLOXYBUTYRIC ACID Chemical Properties,Usage,Production

Uses

4-Benzyloxybutyric acid may be used in the synthesis of benzyloxybutyryl (BOB) esters of alcohols by standard acylation techniques or by the Jacobsen asymmetric nucleophilic ring opening of epoxides.

Synthesis Reference(s)

Tetrahedron, 53, p. 8853, 1997 DOI: 10.1016/S0040-4020(97)90396-3

General Description

4-Benzyloxybutyric acid can be synthesized from γ-butyrolactone. It participates in the asymmetric total synthesis of erythromycin.

Synthesis

(1) Synthesis of 4-benzyloxybutyric acid: 4.0 g (60%, 0.1 mol) of sodium hydride was washed in hexane and mixed with 30 mL of anhydrous DMSO, the resulting mixture was stirred at 60°C in an oil bath for 1 hour. The mixture was cooled to room temperature under nitrogen protection and 100 mL of dry DMSO solution containing 12.6 g (0.1 mol) of sodium 4-hydroxybutyrate was added. After stirring for 2 hours at room temperature, the reaction solution was cooled in an ice bath, 0.2 mol of benzyl bromide was added slowly and the reaction continued for 2 hours at room temperature. After completion of the reaction, 0.5 L of ether was added, the mixture was filtered, the residue was washed with ether (300 mL x 3) and the filtrate was concentrated in vacuum. The concentrated residue was mixed with 100 mL of methanol, 100 mL of 8% sodium hydroxide solution was added, and the mixture was stirred at 60°C for 15 hours. After vacuum drying, the concentrated residue was washed with ether (200 mL x 2) and the ether layer was extracted with 1N sodium hydroxide (50 mL). All aqueous layers were combined and the pH was adjusted to <4 with concentrated hydrochloric acid and then extracted with ether (100 mL x 5). The ether layer was then extracted with 2N sodium hydroxide (50 mL x 3) and all aqueous layers were again neutralized with concentrated hydrochloric acid to pH <4 and extracted with ether. The resulting product was washed with saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated in vacuum to give 9.42 g of 4-benzyloxybutyric acid as a light yellow oil in 49.5% yield.NMR (500 MHz, CDCl3): δ 1.95 (2H, dt, J = 6 and 7 Hz, β-CH2), 2.50 (2H, t, J = 7 Hz, α-CH2), 3.54 (2H, t, J = 6 Hz, γ-CH2), 4.52 (2H, s, PhCH2O), 7.25-7.4 (5H, m, C6H5), 10.0-10.8 (1H, br, CO2H); IR (pure): ν 1710 cm-1 (COOH); FAB-MS: m/z = 195 (M + H+).

References

[1] Patent: US6057431, 2000, A