1,2-Dichloroethane → tert-butyl[(R)-2-(4-butyryl-4-cyclohexylpiperidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]carbamate

HRID 333449Notes

Reaction equation

HRID 333449 reaction equation
[CH:1]1([C:7]2([C:13](=[O:17])[CH2:14][CH2:15][CH3:16])[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:18]([O:22][C:23]([NH:25][C@H:26]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=1)[C:27](O)=[O:28])=[O:24])([CH3:21])([CH3:20])[CH3:19].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[C:18]([O:22][C:23](=[O:24])[NH:25][C@H:26]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=1)[C:27]([N:10]1[CH2:9][CH2:8][C:7]([C:13](=[O:17])[CH2:14][CH2:15][CH3:16])([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[CH2:12][CH2:11]1)=[O:28])([CH3:20])([CH3:21])[CH3:19]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 7017908Boc-O-methyl-D-tyrosineHCID 669878491-(4-Cyclohexylpiperidin-4-yl)butan-1-one

Product 1

HCID 86659316tert-butyl[(R)-2-(4-butyryl-4-cyclohexylpiperidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]carbamateYield 31%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2.1 g (8.9 mmol) of 1-(4-cyclohexylpiperidin-4-yl)butan-1-one, 2.6 g (8.9 mmol) of (R)-2-tert-butoxycarbonylamino-3-(4-methoxyphenyl)propionic acid, 1.88 g (9.8 mmol) of EDC and 1.2 g (9.8 mmol) of HOBT are dissolved in 30 mL of DMF. The mixture is stirred at room temperature for 2 hours. The solution is washed with aqueous 2.5% citric acid solution and extracted with ethyl acetate. The organic phase is washed with aqueous 10N NaOH solution and then dried over sodium sulfate, filtered and concentrated. The crude product is chromatographed on silica gel (eluent: 70/30 heptane/ethyl acetate). 1.4 g of tert-butyl[(R)-2-(4-butyryl-4-cyclohexylpiperidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]carbamate in the form of a colourless oil are obtained in a yield of 31%.

Workup

  1. washThe solution is washed with aqueous 2.5% citric acid solution
  2. extractionextracted with ethyl acetate
  3. washThe organic phase is washed with aqueous 10N NaOH solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product is chromatographed on silica gel (eluent: 70/30 heptane/ethyl acetate)

Sources & evidence

ORD record
ord-c3c4db30796a478fa1d374757937c1e0
Source dataset
uspto-grants-2014_11
Patent number
US08877968B2

Reaction notes

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