Sodium Hydroxide → tert-butyl [(R)-2-[3-(4-benzyloxybutoxy)-3-o-tolylazetidin-1-yl]-1-(4-methoxybenzyl)-2-oxoethyl]carbamate

HRID 530699Notes

Reaction equation

HRID 530699 reaction equation
Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[C:23]([O:27][C:28]([NH:30][C@H:31]([CH2:35][C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=1)[C:32]([OH:34])=O)=[O:29])([CH3:26])([CH3:25])[CH3:24].FC(F)(F)C(O)=O.[CH2:51]([O:58][CH2:59][CH2:60][CH2:61][CH2:62][O:63][C:64]1([C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][C:69]=2[CH3:74])[CH2:67][NH:66][CH2:65]1)[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1.C(N(CC)C(C)C)(C)C.[OH-].[Na+]>CN(C)C=O>[CH2:51]([O:58][CH2:59][CH2:60][CH2:61][CH2:62][O:63][C:64]1([C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][C:69]=2[CH3:74])[CH2:67][N:66]([C:32](=[O:34])[C@H:31]([NH:30][C:28](=[O:29])[O:27][C:23]([CH3:24])([CH3:25])[CH3:26])[CH2:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)[CH2:65]1)[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1

Participants

8

Reactant 6

HCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7017908Boc-O-methyl-D-tyrosineHCID 711523983-(4-Benzyloxybutoxy)-3-o-tolylazetidine trifluoroacetate

Product 1

HCID 86729201tert-butyl [(R)-2-[3-(4-benzyloxybutoxy)-3-o-tolylazetidin-1-yl]-1-(4-methoxybenzyl)-2-oxoethyl]carbamateYield 56.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

778 mg (4 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 544 mg (4 mmol) of N-hydroxybenzotriazole are successively added to a solution of 1 g (3.36 mmol) of (R)-2-tert-butoxycarbonylamino-3-(4-methoxyphenyl)propanoic acid dissolved in 10 ml of N,N-dimethylformamide. After stirring for 15 minutes, 1.5 g (3.36 mmol) of 3-(4-benzyloxybutoxy)-3-o-tolylazetidine trifluoroacetate are added and stirring is continued for 15 minutes at room temperature. 2.34 ml (13.4 mmol) of N,N-diisopropylethylamine are added and the mixture is stirred at room temperature for 2 hours. Aqueous 1N sodium hydroxide solution is added and the reaction medium is extracted twice with ethyl acetate. The organic phase is then washed with aqueous 1N sodium hydroxide and then with aqueous 1N hydrochloric acid solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue obtained is purified by chromatography on silica gel eluted with a heptane/ethyl acetate mixture, the polarity being increased from 100/0 to 70/40. 1.14 g of tert-butyl [(R)-2-[3-(4-benzyloxybutoxy)-3-o-tolylazetidin-1-yl]-1-(4-methoxybenzyl)-2-oxoethyl]carbamate are obtained in the form of a colourless resin, in a yield of 53%.

Workup

  1. stirringstirring
  2. waitis continued for 15 minutes at room temperature
  3. stirringthe mixture is stirred at room temperature for 2 hours
  4. extractionthe reaction medium is extracted twice with ethyl acetate
  5. washThe organic phase is then washed with aqueous 1N sodium hydroxide
  6. dry with materialwith aqueous 1N hydrochloric acid solution, dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude residue obtained
  10. customis purified by chromatography on silica gel
  11. washeluted with a heptane/ethyl acetate mixture
  12. temperaturethe polarity being increased from 100/0 to 70/40

Sources & evidence

ORD record
ord-664622915252481890df9b1d44036c32
Source dataset
uspto-grants-2016_05
Patent number
US09353083B2

Reaction notes

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