3,5-Dichlorobenzaldehyde → (Z)-methyl 2-(benzyloxycarbonylamino)-3-(3,5-dichlorophenyl)acrylate

Step BF (1): To a slurry of N-(Benzyloxycarbonyl)-alpha-phosphonoglycine trimethyl ester (76.37 g, 230.5 mmol) in THF (210 mL) just thawed from a −78° C. bath was added tetramethylguanidine (28.85 mL, 230.0 mmol) dropwise. A cold solution of 3,5-dichlorobenzaldehyde (36.70 g, 209.7 mmol) in THF (52.5 mL) was added via cannula. The cold yellow solution was stirred for 1 hour, at which time TLC revealed no aldehyde remained. The THF was removed in vacuo, and EtOAc and 1M HCl was added. The mixture was extracted three times into EtOAc, and the combined organic layers were washed with water, brine, and then dried over MgSO4. Concentration in vacuo followed by recrystallization of the desired olefin isomer from EtOAc/hexane yielded pure product. Concentration of the mother liquor and recrystallization of the residue yielded, over 4 crops, 68.22 g (86% yield) of (Z)-methyl 2-(benzyloxycarbonylamino)-3-(3,5-dichlorophenyl)acrylate. 1H NMR (500 MHz, CDCl3) δ 7.28-7.42 (m, 7H) 7.16 (s, 2H) 6.55 (s, 1H) 5.10 (s, 2H) 3.79-3.90 (m, 3H).

1. customjust thawed from a −78° C.
2. customThe THF was removed in vacuo, and EtOAc and 1M HCl
3. additionwas added
4. extractionThe mixture was extracted three times into EtOAc
5. washthe combined organic layers were washed with water, brine
6. dry with materialdried over MgSO4
7. concentrationConcentration in vacuo
8. customfollowed by recrystallization of the desired olefin isomer from EtOAc/hexane yielded pure product
9. customConcentration of the mother liquor and recrystallization of the residue

ORD record

ord-071854fcd62540b5b6c50979d18fa5d3

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07772221B2