1,2-Dichloroethane → [2-(3-butoxy-3-o-tolyl-azetidin-1-yl)-1-(4-hydroxybenzyl)-2-oxoethyl]-3-(3H-imidazol-4-yl)propionamide

HRID 540419Notes

Reaction equation

HRID 540419 reaction equation
[CH2:1](Cl)[CH2:2]Cl.C1C=CC2N(O)N=[N:11]C=2C=1.C(OC(N[C@H:23]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([OH:34])=[CH:30][CH:29]=1)[C:24]([OH:26])=O)=O)(C)(C)C.FC(F)(F)C(O)=O.[CH2:42]([O:46][C:47]1([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=2[CH3:57])[CH2:50][NH:49][CH2:48]1)[CH2:43][CH2:44][CH3:45].C([N:60]([CH2:63]C)[CH2:61][CH3:62])C.Cl.C[N:67](C)[CH:68]=[O:69]>>[CH2:42]([O:46][C:47]1([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=2[CH3:57])[CH2:48][N:49]([C:24](=[O:26])[CH:23]([CH:1]([CH2:2][C:62]2[NH:11][CH:63]=[N:60][CH:61]=2)[C:68]([NH2:67])=[O:69])[CH2:27][C:28]2[CH:29]=[CH:30][C:31]([OH:34])=[CH:32][CH:33]=2)[CH2:50]1)[CH2:43][CH2:44][CH3:45]

Participants

8

Reactant 7

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 1549481(2R)-2-(((tert-butoxy)carbonyl)amino)-3-(4-hydroxyphenyl)propanoic acidHCID 669880653-Butoxy-3-o-tolylazetidine trifluoroacetate

Product 1

HCID 66988077[2-(3-butoxy-3-o-tolyl-azetidin-1-yl)-1-(4-hydroxybenzyl)-2-oxoethyl]-3-(3H-imidazol-4-yl)propionamideYield 90%

Procedure

205 mg (1.1 mmol) of EDC and then 145 mg (1.1 mmol) of HOBt are added to a solution of 250 mg (0.9 mmol) of (R)-2-tert-butoxycarbonylamino-3-(4-hydroxyphenyl)-propanoic acid in 5 ml of dimethylformamide. After stirring for 15 minutes at ambient temperature, 300 mg (1.1 mmol) of 3-butoxy-3-o-tolylazetidine trifluoro-acetate (described in Example 15.5) and 0.5 ml (3.6 mmol) of triethylamine are added. The reaction medium is stirred for 2 h at ambient temperature and then a 1N aqueous solution of hydrochloric acid is added and the mixture is extracted with ethyl acetate. The organic phase is washed with water, and then dried over magnesium sulphate, filtered and evaporated. The residue is purified by silica gel chromatography, elution being carried out with a 60/40 heptane/ethyl acetate mixture. 410 mg of [2-(3-butoxy-3-o-tolyl-azetidin-1-yl)-1-(4-hydroxybenzyl)-2-oxoethyl]-3-(3H-imidazol-4-yl)propionamide are obtained with a yield of 90%.

Workup

  1. stirringThe reaction medium is stirred for 2 h at ambient temperature
  2. extractionthe mixture is extracted with ethyl acetate
  3. washThe organic phase is washed with water
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue is purified by silica gel chromatography, elution

Sources & evidence

ORD record
ord-7b3897ad785c40c2aa417f05a9557aaa
Source dataset
uspto-grants-2014_10
Patent number
US08871187B2

Reaction notes

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