1,2-Dichloroethane → tert-butyl[(R)-2-(3-cyclohexyl-3-pentylazetidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]carbamate

HRID 540402Notes

Reaction equation

HRID 540402 reaction equation
[CH2:1](Cl)CCl.C1C=C[C:8]2N(O)N=N[C:9]=2[CH:10]=1.C(O[C@:20]([N:33]=C=O)([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=1)[C:21]([OH:23])=O)(C)(C)C.[C:36]([OH:41])(=[O:40])C(O)=O.[CH:42]1([C:48]2([CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[CH2:51][NH:50][CH2:49]2)[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1.C(N(CC)CC)C>CN(C=O)C>[C:9]([O:41][C:36](=[O:40])[NH:33][C@H:20]([CH2:24][C:25]1[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=1)[C:21]([N:50]1[CH2:49][C:48]([CH:42]2[CH2:43][CH2:44][CH2:45][CH2:46][CH2:47]2)([CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[CH2:51]1)=[O:23])([CH3:8])([CH3:10])[CH3:1]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 669884153-Cyclohexyl-3-pentylazetidine oxalateHCID 87226379(R)-2-tert-butoxy-carbonylamino-3-(4-methoxyphenyl)propionic acid

Product 1

HCID 67295580tert-butyl[(R)-2-(3-cyclohexyl-3-pentylazetidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]carbamateYield 59%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.36 g (1.98 mmol) of EDC, 0.25 g (1.85 mmol) of HOBt and 0.51 g (1.73 mmol) of (R)-2-tert-butoxy-carbonylamino-3-(4-methoxyphenyl)propionic acid are added to 0.43 g (1.69 mmol) of 3-cyclohexyl-3-pentylazetidine oxalate dissolved in 8 ml of DMF. After 5 minutes, 0.9 ml (6.5 mmol) of triethylamine is added. After 1 hour 30 minutes, the reaction medium is extracted with a 1/1 EtOAc/heptane mixture and washed with a solution of 1N hydrochloric acid, of 1N sodium hydroxide and of water. The organic phase is dried over MgSO4, filtered and concentrated. The residue is purified on a silica column (eluent 6/4 heptane/EtOAc). 0.48 g of tert-butyl[(R)-2-(3-cyclohexyl-3-pentylazetidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]carbamate in the form of a colourless oil is obtained with a yield of 59%.

Workup

  1. waitAfter 1 hour 30 minutes
  2. extractionthe reaction medium is extracted with a 1/1 EtOAc/heptane mixture
  3. washwashed with a solution of 1N hydrochloric acid, of 1N sodium hydroxide and of water
  4. dry with materialThe organic phase is dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified on a silica column (eluent 6/4 heptane/EtOAc)

Sources & evidence

ORD record
ord-052580eb1ec047bab8c0e9dd42a8ff73
Source dataset
uspto-grants-2014_10
Patent number
US08871187B2

Reaction notes

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