1,2-Dichloroethane → Tert-butyl[2-(3-butoxy-3-o-tolyl-azetidin-1-yl)-1-(2-hydroxy-4-methoxybenzyl)-2-oxo-ethyl]carbamate

HRID 540415Notes

Reaction equation

HRID 540415 reaction equation
C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[C:15]([O:19][C:20]([NH:22][CH:23]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:29]=1[OH:36])[C:24]([OH:26])=O)=[O:21])([CH3:18])([CH3:17])[CH3:16].FC(F)(F)C(O)=O.[CH2:44]([O:48][C:49]1([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=2[CH3:59])[CH2:52][NH:51][CH2:50]1)[CH2:45][CH2:46][CH3:47].C(N(C(C)C)CC)(C)C.Cl>CN(C)C=O>[C:15]([O:19][C:20](=[O:21])[NH:22][CH:23]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:29]=1[OH:36])[C:24]([N:51]1[CH2:50][C:49]([O:48][CH2:44][CH2:45][CH2:46][CH3:47])([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=2[CH3:59])[CH2:52]1)=[O:26])([CH3:16])([CH3:17])[CH3:18]

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 669880653-Butoxy-3-o-tolylazetidine trifluoroacetateHCID 669881482-Tert-butoxycarbonylamino-3-(2-hydroxy-4-methoxy-phenyl)propanoic acid

Product 1

HCID 131731974Tert-butyl[2-(3-butoxy-3-o-tolyl-azetidin-1-yl)-1-(2-hydroxy-4-methoxybenzyl)-2-oxo-ethyl]carbamateYield 143.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

74 mg (0.4 mmol) of EDC and 52 mg (0.4 mmol) of HOBt are added to a solution of 100 mg (0.3 mmol) of 2-tert-butoxycarbonylamino-3-(2-hydroxy-4-methoxyphenyl)-propanoic acid in 5 ml of dimethylformamide. The mixture is stirred for 15 min and 107 mg (0.3 mmol) of 3-butoxy-3-o-tolylazetidine trifluoroacetate are added. After stirring for a further 15 minutes at ambient temperature, 0.3 ml (1.3 mmol) of diisopropylethylamine is added. The reaction medium is stirred for 2 h, and then 10 ml of a 1N aqueous solution of hydrochloric acid are added and the medium is extracted with ethyl acetate. The organic phase is washed with water and then dried over magnesium sulphate, filtered and evaporated. The residue is filtered through silica gel (eluent: 70/30 heptane/ethyl acetate). 220 mg of tert-butyl[2-(3-butoxy-3-o-tolylazetidin-1-yl)-1-(2-hydroxy-4-methoxybenzyl)-2-oxoethyl]carbamate are obtained in the form of a yellow oil and are used crude in the next stage.

Workup

  1. stirringAfter stirring for a further 15 minutes at ambient temperature
  2. stirringThe reaction medium is stirred for 2 h
  3. extractionthe medium is extracted with ethyl acetate
  4. washThe organic phase is washed with water
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. customevaporated
  8. filtrationThe residue is filtered through silica gel (eluent: 70/30 heptane/ethyl acetate)

Sources & evidence

ORD record
ord-e4e8cf951bd842b7aba61fce3df860be
Source dataset
uspto-grants-2014_10
Patent number
US08871187B2

Reaction notes

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