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

HRID 501743Notes

Reaction equation

HRID 501743 reaction equation
C(O[C@H]1C2C(=CC(OCCC)=CC=2)[C@@H](N)C1)C=C.[CH3:19][O:20][C:21]([CH:23](P(OC)(OC)=O)[NH:24][C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])=[O:22].CN(C)C(=N)N(C)C.[Cl:49][C:50]1[CH:51]=[C:52]([CH:55]=[C:56]([Cl:58])[CH:57]=1)[CH:53]=O>C1COCC1>[CH2:28]([O:27][C:25]([NH:24]/[C:23](=[CH:53]\[C:52]1[CH:51]=[C:50]([Cl:49])[CH:57]=[C:56]([Cl:58])[CH:55]=1)/[C:21]([O:20][CH3:19])=[O:22])=[O:26])[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

6

Reactant 4

HCID 357463,5-DichlorobenzaldehydeHCID 664601,1,3,3-TetramethylguanidineHCID 2734718Methyl 2-{[(benzyloxy)carbonyl]amino}-2-(dimethyl phosphono)acetateHCID 59423826(1S,3R)-3-(Allyloxy)-6-propoxy-2,3-dihydro-1H-inden-1-amine

Product 1

HCID 68461432(Z)-methyl 2-(benzyloxycarbonylamino)-3-(3,5-dichlorophenyl)acrylateYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-071854fcd62540b5b6c50979d18fa5d3
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Reaction notes

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