(2R,4R)-N-Boc-4-hydroxypyrrolidine-2-carboxylic acid Chemical Properties

Melting point:

146-151 °C

alpha 

+48～+52°(c=0.67,MeOH,24℃)

Boiling point:

390.9±42.0 °C(Predicted)

Density 

1.312

storage temp. 

2-8°C

pka

3.80±0.40(Predicted)

form 

powder to crystal

color 

White to Light yellow

optical activity

[α]22/D +50.0°, c = 1 in methanol

InChIKey

BENKAPCDIOILGV-RNFRBKRXSA-N

Safety Information

Hazard Codes 

Xi

Risk Statements 

36

Safety Statements 

26

WGK Germany 

3

HazardClass 

IRRITANT

HS Code 

29339900

(2R,4R)-N-Boc-4-hydroxypyrrolidine-2-carboxylic acid Usage And Synthesis

Chemical Properties

White solid

Uses

N-Boc-cis-4-hydroxy-D-proline can be used:

• As a starting material in the synthesis of DNA mimicking pyrrolidine peptide nucleic acid (PNA) analog.
• In the synthesis of biologically important macrocyclic dilactones.
• As an intermediate in the synthesis of histamine H₃?receptor antagonists.

Synthesis

(2R,4R)-4-Hydroxypyrrolidine-2-carboxylic acid hydrochloride (0.50 g, 3.0 mmol) was dissolved in 6 mL of THF/H2O (2:1) mixed solvent, followed by the addition of 10% NaOH aqueous solution (1.25 mL) for neutralization. Next, di-tert-butyl dicarbonate (0.95 g, 4.42 mmol) was added to the reaction system. The reaction mixture was stirred at room temperature overnight and then the THF was removed by rotary evaporator.The residue was adjusted to pH 2 with 10% aqueous KHSO4 solution and then extracted with ethyl acetate several times. The organic phases were combined, washed sequentially with water and saturated saline and dried over anhydrous Na2SO4. The solvent was concentrated under reduced pressure to give (2R,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid (542 mg, 78%) as a slurry, which was used directly in the next step of the reaction. [α]D25 = +15.3 (c 1.02, MeOH). IR (thin film method): νmax 3462, 2976, 2934, 1740, 1639 cm?1. 1H NMR (400 MHz, CDCl3) δ 7.22 (br s, 1H), 5.11-5.09 (m, 2H), 4.94-4.93 (m, 1H) , 4.40 (s, 1H), 3.64-3.62 (m, 1H), 3.49-3.44 (m, 2H), 2.27-1.90 (s, 9H).13C NMR (100 MHz, CDCl3) δ 172.47, 151.74, 75.81, 67.15, 55.24, 52.27, 35.97, 25.63 ppm. HRMS (ESI): m/z [M + H]+ calcd for C10H18NO5 232.1185; found 232.1171.

IC 50

Non-cleavable Linker

References

[1] Journal of Medicinal Chemistry, 2018, vol. 61, # 3, p. 681 - 694
[2] Journal of the American Chemical Society, 2013, vol. 135, # 11, p. 4333 - 4363
[3] Tetrahedron Asymmetry, 2015, vol. 26, # 20, p. 1156 - 1166
[4] Patent: TW2017/8221, 2017, A. Location in patent: Page/Page column 92; 93

(2R,4R)-N-Boc-4-hydroxypyrrolidine-2-carboxylic acid(135042-12-5)Related Product Information

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