(R)-PIPERIDIN-2-YLMETHYL-CARBAMIC ACID TERT-BUTYL ESTER

(R)-PIPERIDIN-2-YLMETHYL-CARBAMIC ACID TERT-BUTYL ESTER Property

Boiling point:

321.8±15.0 °C(Predicted)

Density 

0.981±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

form 

solid

pka

12.84±0.46(Predicted)

Appearance

White to off-white Solid

optical activity

11.71°(C=0.77g/100mI, CHCL3, 20°C, 589nm)

InChI

InChI=1S/C11H22N2O2/c1-11(2,3)15-10(14)13-8-9-6-4-5-7-12-9/h9,12H,4-8H2,1-3H3,(H,13,14)/t9-/m0/s1

InChIKey

DIRUVVRMWMDZAE-VIFPVBQESA-N

SMILES

C(OC(C)(C)C)(=O)NC[C@@H]1CCCCN1

Safety

HS Code 

2933399990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H315Causes skin irritation

H318Causes serious eye damage

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

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

P310Immediately call a POISON CENTER or doctor/physician.

(R)-PIPERIDIN-2-YLMETHYL-CARBAMIC ACID TERT-BUTYL ESTER Chemical Properties,Usage,Production

Uses

Chiral building block developed using Liverpool ChiroChem-patented technology.

Synthesis

The general procedure for the synthesis of tert-butyl (S)-(piperidin-2-ylmethyl)carbamate using the compound (CAS:248914-23-0) as starting material was as follows: all weights and volumes were calculated based on the amount of Intermediate 1. First, palladium carbon catalyst (0.15 wt%, 10% Pd/C, Johnson Matthey paste type 490) and acetic acid (0.73 v/v) were added to a THF solution of Intermediate 3. The hydrogenation reaction was carried out at 1200-1300 mbar and 40 °C under nitrogen protection. The conversion was completed after 21 hours of reaction. The catalyst was removed by filtration and the filter cake was washed with THF (2 x 2.2 v/v). The filtrates were combined and concentrated to about 2.8 volumes at 50°C jacket temperature and under reduced pressure. Toluene (2.6 volumes) was added and distillation was continued under reduced pressure and again concentrated to about 2.8 volumes. Subsequently, toluene (5 volumes) was added and extracted with aqueous citric acid (3 x 3 volumes; citric acid concentration: 450 g/L). The aqueous layers were combined and back-extracted with toluene (4 x 5 volumes). The pH of the aqueous layer was adjusted to >10 by the addition of 30% NaOH solution (~6.5 vol), and then the product was extracted with THF (3 × 5 vol). The organic layers were combined and dried with sodium sulfate (2 wt%). The sodium sulfate was removed by filtration and the filter cake was washed with THF (2 x 1.3 v/v). The filtrates were combined and concentrated to 4.25 volumes at 50°C jacket temperature and under reduced pressure. Methylcyclohexane (3 x 4.3 volumes) was added in three portions and distillation was continued. The solvent was further removed under reduced pressure (3 x 4.3 volumes). Methylcyclohexane (0.53 volume) was added and the suspension was cooled to -10°C over 4 hours and stirred at this temperature for 12 hours. The slurry was filtered, washed with pre-cooled methylcyclohexane (0.66 v/v, -10 to -5 °C) and dried at 50 °C jacket temperature to give tert-butyl (S)-(piperidin-2-ylmethyl)carbamate as a white solid. The calibration yield was 87% of the theoretical value.

References

[1] Patent: WO2009/34133, 2009, A1. Location in patent: Page/Page column 14-15
[2] Heterocycles, 1999, vol. 51, # 9, p. 2065 - 2072