Diisobutylaluminumhydride → HCID 71437553, compound

To a stirring, cold (−10° C.) solution of ethyl 4-(tert-butoxycarbonylamino)-2-fluorobut-2-enoate (a 10:1 mixture of EIZ isomers; 6.33 g, 25.6 mmol) in CH2Cl2 (200 mL) under Ar was added dropwise Diisobutylaluminium hydride solution (1M solution in hexanes, 70.5 mL, 70.49 mmol). After addition was complete the reaction was left to stir at this temperature for a further 2 h. The reaction was then quenched carefully by dropwise addition of cold water. The resulting slurry was poured into a flask containing a saturated aqueous solution of sodium potassium tartrate (400 mL) and the biphasic mixture was stirred vigorously for 2 h. After transferring the mixture to a separatory funnel the aqueous phase was extracted with CH2Cl2 (3×100 mL). The combined organics were washed with brine (100 mL), dried over anhydrous MgSO4 and concentrated in vacuo to give tert-butyl-3-fluoro-4-hydroxybut-2-enylcarbamate as a 10:1 mixture of E/Z isomers. Purification and separation of the desired E isomer was performed using silica gel chromatography eluting with 30% ethyl acetate in hexanes affording (E)-tert butyl-3-fluoro-4-hydroxybut-2-enylcarbamate (4.25 g, 20.7 mmol, 81%) as a colourless oil that solidified upon cooling, 1H-NMR (200 MHz, CDCl3): δppm: 1.43 (9H, s), 3.72 (2H, dd, J 7.5, 5.4 Hz), 4.25 (2H, d, J 21.5 Hz), 4.85 (1H, br s), 5.18 (1H, dt, 19.2, 8.5 Hz).

1. additionAfter addition
2. waitwas left
3. customThe reaction was then quenched carefully by dropwise addition of cold water
4. additionThe resulting slurry was poured into a flask
5. additioncontaining a saturated aqueous solution of sodium potassium tartrate (400 mL)
6. stirringthe biphasic mixture was stirred vigorously for 2 h
7. extractionwas extracted with CH2Cl2 (3×100 mL)
8. washThe combined organics were washed with brine (100 mL)
9. dry with materialdried over anhydrous MgSO4
10. concentrationconcentrated in vacuo

ORD record

ord-64466233ebda48b98962f96be8a76f2a

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426587B2