反应 #80455

反应方程式

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

收率 64.0%

溶剂

isopropylacetate

Heptane

反应条件

后处理

1. 1
   workup.STIRRINGstirred for 20 min
2. 2
   温度the mixture was cooled in an ice-water bath
3. 3
   workup.STIRRINGstirred for 15 min
4. 4
   过滤The solid was filtered off
5. 5
   洗涤washed with H2O, heptane, 25% CH2Cl2 /heptane
6. 6
   其他dried in vauco

实验过程

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.

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