1-BOC-4-FLUORO-4-(HYDROXYMETHYL)-PIPERIDINE Chemical Properties

Boiling point:

311.0±27.0 °C(Predicted)

Density 

1.13±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

pka

14.94±0.10(Predicted)

Appearance

Colorless to off-white Solid-Liquid Mixture

InChI

InChI=1S/C11H20FNO3/c1-10(2,3)16-9(15)13-6-4-11(12,8-14)5-7-13/h14H,4-8H2,1-3H3

InChIKey

BWZOULIMVKCGII-UHFFFAOYSA-N

SMILES

N1(C(OC(C)(C)C)=O)CCC(F)(CO)CC1

Safety Information

HS Code 

2933399990

1-BOC-4-FLUORO-4-(HYDROXYMETHYL)-PIPERIDINE Usage And Synthesis

Uses

tert-Butyl 4-Fluoro-4-(hydroxymethyl)piperidine-1-carboxylate is used in preparation of heterocyclic compounds as BCL 2 inhibitors.

Synthesis

General procedure for the synthesis of 1-Boc-4-fluoro-4-(hydroxymethyl)piperidine from 1-oxa-6-azaspiro[2.5]octane-6-carboxylic acid tert-butyl ester: Commercially available epoxide (2 g, 9.38 mmol) was dissolved in 10 mL of dichloromethane, and added slowly and dropwise to a pre-cooled to -10°C 0.6 mL solution of HF pyridinium fluoride (70%) in a 10 mL dichloromethane to a mixture of 0.6 mL HF pyridinium fluoride (70%) and 10 mL methylene chloride. The reaction mixture was kept at -10°C. After the dropwise addition was completed, the reaction system was warmed to room temperature and stirred continuously for 4 hours. Upon completion of the reaction, the reaction mixture was diluted with dichloromethane and subsequently washed with saturated aqueous sodium carbonate solution. The organic phase was separated, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to remove the solvent to give the crude product. Purification by silica gel column chromatography with ethyl acetate/heptane (20% to 50%) as eluent afforded 1-Boc-4-fluoro-4-(hydroxymethyl)piperidine as a pale yellow oil (1.44 g, 66% yield).1H-NMR (400 MHz, CDCl3) data: δ=1.44 (s, 9H), 1.47-1.63 (m, 2H). 1.85 (m, 2H), 3.08 (m, 2H), 3.56 (s, 1H), 3.61 (s, 1H), 3.92 (brs, 2H). ms ESI: m/z=233.98 (M+).

References

[1] Patent: US2011/256064, 2011, A1. Location in patent: Page/Page column 19; 20
[2] Patent: EP2377860, 2011, A1. Location in patent: Page/Page column 26
[3] Patent: EP1505067, 2005, A1. Location in patent: Page/Page column 368; 369
[4] Journal of Medicinal Chemistry, 2008, vol. 51, # 13, p. 3692 - 3695
[5] Patent: WO2004/5255, 2004, A1. Location in patent: Page 26-27

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