Reaktion #80455

Reaktionsgleichung

diisopropylamine

NH4OH

(R)-N-hydroxy-N-(3-butyn-2-yl)urea

2-iodo-5-(4-fluorophenylmethyl)thiophene

→

(R)-N-{3-[5-(4-fluorophenylmethyl)thien-2-yl]-1-methyl-2-propynyl)-N-hydroxyurea

Ausbeute 64.0%

Lösungsmittel

isopropylacetate

Heptane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirred for 20 min
2. 2
   Temperaturthe mixture was cooled in an ice-water bath
3. 3
   workup.STIRRINGstirred for 15 min
4. 4
   FiltrationThe solid was filtered off
5. 5
   Waschenwashed with H2O, heptane, 25% CH2Cl2 /heptane
6. 6
   Sonstigedried in vauco

Vorschrift

To the (R)-N-hydroxy-N-(3-butyn-2-yl)urea prepared in step 3 above was added a solution of 2-iodo-5-(4-fluorophenylmethyl)thiophene (45 mmol), in isopropylacetate, followed by diisopropylamine (10 mL, 7.2 g, 71 mmol), bis(acetonitrile)palladium(II) chloride (65 mg, 0.25 mmol), copper(I)iodide (95 mg, 0.50 mmol), and triphenylphosphine (131 mg, 0.50 mmol), and the reaction mixture was stirred under nitrogen at ambient temperature for 2 hours. The reaction mixture was poured into 20% aqueous NH4OH (200 mL) and stirred for 20 min. Heptane (300 mL) was added and the mixture was cooled in an ice-water bath and stirred for 15 min. The solid was filtered off, washed with H2O, heptane, 25% CH2Cl2 /heptane, and dried in vauco to give 10.2 g (64% yield from (S)-O-p-toluenesulfonyl-3-butyn-2-ol) of (R)-N-{3-[5-(4-fluorophenylmethyl)thien-2-yl]-1-methyl-2-propynyl)-N-hydroxyurea (98% ee by chiral HPLC). m.p. 135°-136° C.(dec). 1H NMR (DMSO-d6, 300 MHz) δ1.32 (d, J=6.0 Hz, 3H), 4.11 (s, 2H), 5.10 (q, J=6.0 Hz, 1H), 6.54 (s, 2H), 6.81 (d, J=3.0 Hz, 1H), 7.08 (d, J=3.0 Hz, 1H), 7.10-7.18 (m, 2H), 7.25-7.32 (m, 2H), 9.33 (s, 1H). MS (DCI/NH3) m/e 319 (M+H)+. [α]D23° =+47.8° (C=1 MeOH). Anal calcd for C16H15FN2O2S: C, 60.36; H, 4.75; N, 8.80. Found: C, 60.31; H, 4.79; N, 8.50.

Quelle