تفاعل #609541

معادلة التفاعل

DIPEA

triphosgene

HCl

(1R,2S)-2-(but-3-en-1-yl)cyclopentanol

3-methyl-L-valine

NaOH

→

desired product

N-({[(1R,2S)-2-(but-3-en-1-yl)cyclopentyl]oxy}carbonyl)-3-methyl-L-valine

المذيبات

1,4-dioxane

dioxane

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGstirred at 70° C. for 15 hours
2. 2
   أخرىAt 22° C.
3. 3
   استخلاصextracted with (3×100 ml) ether
4. 4
   غسيلThe combined organic layer were washed with water (100 ml), brine (70 ml)
5. 5
   تجفيفdried over Na2SO4
6. 6
   ترشيحfiltered
7. 7
   تركيزconcentrated
8. 8
   أخرىThe residue was purified by flash chromatography (silica gel, eluting with 10 to 100% EtOAc in hexane)

الإجراء التجريبي

To a stirred solution of (1R,2S)-2-(but-3-en-1-yl)cyclopentanol (see International Patent Application Publication No. WO2009/134624) (2.1 g) and DIPEA (5.3 mL) in anhydrous 1,4-dioxane (51 ml), at 10° C. and under nitrogen, was added a solution of triphosgene (1.5 g) in dioxane (51 ml). This reaction was stirred at 22° C. for 1.5 hour and 3-methyl-L-valine (2 g) and NaOH (1M, 30.5 mL) were added, then stirred at 70° C. for 15 hours. At 22° C., the reaction solution was acidified to pH 3 with 1 N HCl and extracted with (3×100 ml) ether. The combined organic layer were washed with water (100 ml), brine (70 ml), dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (silica gel, eluting with 10 to 100% EtOAc in hexane) to give the desired product (3.26 g). LRMS (ES+) M/Z (M+Na)+ 320.1.

المصدر