반응 #467773

반응 방정식

triethyl-2-fluoro-2-phophonoacetate

1,8-diazabicyclo[5.4.0]undec-7-ene

N-Boc-piperidine-4-carboxaldehyde

Lithium chloride

lithium chloride

→

(E)-ethyl 2-fluoro-3-(N-Boc-piperdin-4-yl)propenoate

용매

acetonitrile

acetonitrile

반응 조건

후처리

1. 1
   기타Intermediate AE1 was prepared
2. 2
   workup.DISSOLUTIONwas dissolved
3. 3
   기타to form a homogeneous solution
4. 4
   기타The reaction was quenched with saturated ammonium chloride (20 mL)
5. 5
   workup.ADDITIONdiluted with ethyl acetate (150 mL)
6. 6
   세척washed with saturated sodium chloride (50 mL)
7. 7
   건조The organic layer was dried (magnesium sulfate)
8. 8
   기타evaporated

실험 절차

Compound 9 was prepared using the methods described in Scheme AE. Intermediate AE1 was prepared as follows. Lithium chloride (0.39 g) was added to a solution cooled to 0° C. of triethyl-2-fluoro-2-phophonoacetate (1.84 mL) and 1,8-diazabicyclo[5.4.0]undec-7-ene (1.15 mL) in acetonitrile (6 mL). The mixture was stirred until the lithium chloride was dissolved to form a homogeneous solution. N-Boc-piperidine-4-carboxaldehyde (1.61 g) in acetonitrile (2.0 mL) was added to the mixture and stirred for 24 h at room temperature. The reaction was quenched with saturated ammonium chloride (20 mL), diluted with ethyl acetate (150 mL), and washed with saturated sodium chloride (50 mL). The organic layer was dried (magnesium sulfate) and evaporated to yield 2.27 g of (E)-ethyl 2-fluoro-3-(N-Boc-piperdin-4-yl)propenoate (AE1). AE1 was carried forward as shown in Scheme AA to afford 9. Compound 9 was isolated as white flakes: mp 147-150° C.; MS m/e 515 (MH+). Anal. calcd. for C25H31FN6O5•2.3 HCl•1.6 H2O (627.25): C, 47.88; H, 5.87; N, 13.40; Cl, 13.00. Found: C, 48.26; H, 6.02; N, 12.90; Cl, 12.74.

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