Hydrochloric Acid → (R)-N-hydroxy-N-(3-butyn-2-yl)urea

To a solution of (S)-O-p-toluenesulfonyl-3-butyn-2-ol (11.2 g, 50.0 mmol), prepared by addition of p-toluenesulfonyl chloride and triethylamine to (S)-3-butyn-2-ol, in methanol (100 mL), was added 55% aqueous hydroxylamine (30 mL, 0.50 mol) and the reaction mixture was stirred at ambient temperature for 40 hours. The reaction mixture was cooled to 10° C. and concentrated HCl (50 mL) was added dropwise. The reaction mixture was concentrated in vacuo and the residue was partitioned between H2O (50 mL) and ethyl acetate (200 mL). The 2-phase mixture was cooled to 10° C. and taken to pH 8 with 50% aqueous NaOH solution (60 mL). After stirring for 15 min the layers were separated and the aqueous phase was extracted twice with 200 mL of ethyl acetate. The combined ethyl acetate extracts were cooled to 10° C. and a solution of KOCN (8.1 g, 0.10 mmol) in H 2 O (30 mL) was added, followed by dropwise addition of 11 mL of concentrated HCl, and the reaction mixture was stirred for 30 min. The ethyl acetate layer was separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give 5.9 g (92% yield) of (R)-N-hydroxy-N-(3-butyn-2-yl)urea. mp 129° C. [α]D24 =+53.3° (c=0.58, CH3OH). 1H NMR (DMSO-d6, 300 MHz) 67 1.25 (d, 3H, J=7 Hz), 3.05 (d, 1H, J=2.5 Hz), 4.85 (dq, 1H, J=2.5, 7 Hz), 6.50 (br s, 2H), 9.24 (s, 1H). 13CNMR (DMSO-d6, 75 MHz) δ18.43, 45.14, 72.81, 83.87, 161.51. IR (KBr) 3455, 3330, 3290, 3215, 1658, 1637, 1585 cm-1. MS (DCI/NH3 ) m/e 146 (M+NH4)+, 163 (M+NH4.NH3)+. Anal. Calc for C5H8N2O2 : C, 46.87; H, 6.29; N, 21.86. Found: C, 46.78; H, 6.34; N, 21.72.

1. temperatureThe reaction mixture was cooled to 10° C.
2. concentrationThe reaction mixture was concentrated in vacuo
3. customthe residue was partitioned between H2O (50 mL) and ethyl acetate (200 mL)
4. temperatureThe 2-phase mixture was cooled to 10° C.
5. stirringAfter stirring for 15 min the layers
6. customwere separated
7. extractionthe aqueous phase was extracted twice with 200 mL of ethyl acetate
8. temperatureThe combined ethyl acetate extracts were cooled to 10° C.
9. stirringthe reaction mixture was stirred for 30 min
10. customThe ethyl acetate layer was separated
11. extractionthe aqueous layer was extracted twice with ethyl acetate
12. dry with materialThe combined organic layers were dried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated in vacuo

ORD record

ord-7d0e47acb2814b34bc4376059c5f7d54

Source dataset

uspto-grants-1996_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05506261