3-azetidinecarboxylic Acid → 1-{4-[3(5-Ethyl-4-phenyl-thiophen-2-yl)-3-oxo-propyl]benzyl}azetidine-3-carboxylic acid

HRID 552285Notes

Reaction equation

HRID 552285 reaction equation
[CH2:1]([C:3]1[S:7][C:6]([C:8](=[O:19])[CH:9]=[CH:10][C:11]2[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=2)=[CH:5][C:4]=1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH3:2].[NH:26]1[CH2:29][CH:28]([C:30]([OH:32])=[O:31])[CH2:27]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C1COCC1.CO.C(Cl)Cl.CN(C=O)C.CO.[Pd]>[CH2:1]([C:3]1[S:7][C:6]([C:8](=[O:19])[CH2:9][CH2:10][C:11]2[CH:18]=[CH:17][C:14]([CH2:15][N:26]3[CH2:29][CH:28]([C:30]([OH:32])=[O:31])[CH2:27]3)=[CH:13][CH:12]=2)=[CH:5][C:4]=1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH3:2]

Participants

9

Reactant 3

HCID 931923-azetidinecarboxylic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 866401734-[(5-Ethyl-4-phenyl-thiophen-2-yl)-3-oxo-propenyl]-benzaldehyde

Product 1

HCID 592489831-{4-[3(5-Ethyl-4-phenyl-thiophen-2-yl)-3-oxo-propyl]benzyl}azetidine-3-carboxylic acidYield 8.5%

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 21901440N,N-dimethylformamide methanolSolvent

Procedure

A solution of 4-[(5-ethyl-4-phenyl-thiophen-2-yl)-3-oxo-propenyl]-benzaldehyde (140 mg, 0.405 mmol) and azetidine-3-carboxylic acid (51 mg, 0.506 mmol) and NaBH(OAc)3 (257 mg, 1.21 mmol) in THF (6 mL) is stirred at rt for 6 h. The reaction mixture is diluted with a small amount of methanol and DCM (150 mL) and washed with water. The organic phase is separated and the aqueous phase again extracted with DCM. The combined organic extracts are dried over MgSO4 and evaporated. The residue is suspended in methanol, filtered and dried. The solid material obtained is suspended in DMF/methanol and treated with Pd/C (20 mg, 10% Pd). The slurry is stirred under 1.5 bar of H2 at rt for 16 h. The mixture is filtered and the filtrate is evaporated and dried to give 1-{4-[3(5-ethyl-4-phenyl-thiophen-2-yl)-3-oxo-propyl]benzyl}azetidine-3-carboxylic acid (15 mg) as a colourless solid; LC-MS: tR=0.89 min, [M+1]+=434.17.

Workup

  1. washwashed with water
  2. customThe organic phase is separated
  3. extractionthe aqueous phase again extracted with DCM
  4. dry with materialThe combined organic extracts are dried over MgSO4
  5. customevaporated
  6. filtrationfiltered
  7. customdried
  8. customThe solid material obtained
  9. filtrationThe mixture is filtered
  10. customthe filtrate is evaporated
  11. customdried

Sources & evidence

ORD record
ord-8756b2e7499f4c709d54f901ab6a6bc8
Source dataset
uspto-grants-2011_05
Patent number
US07951794B2

Reaction notes

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