1,2-Dichloroethane → N-(2-Benzyloxy-1-carbamoyl-ethyl)-2-cyclohexylmethyl-4-morpholin-4-yl-oxo-butyramide

HRID 480228Notes

Reaction equation

HRID 480228 reaction equation
[CH:1]1([CH2:7][C@H:8]([CH2:12][C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=O)[C:9]([OH:11])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)CCl.[OH:25]N1C2C=CC=CC=2N=N1.Cl.[CH2:36]([O:43][CH2:44][C@@H:45]([C:47]([NH2:49])=[O:48])[NH2:46])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.CN1CCOCC1>CN(C=O)C.CCOC(C)=O>[CH2:36]([O:43][CH2:44][CH:45]([NH:46][C:9](=[O:11])[CH:8]([CH2:7][CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1)[C:12](=[O:25])[CH2:13][N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)[C:47](=[O:48])[NH2:49])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 11084744O-benzyl-L-serineamideHCID 59972959(R)-2-Cyclohexylmethyl-4-morpholin-4-yl-4-oxo-butyric acid

Product 1

HCID 18768922N-(2-Benzyloxy-1-carbamoyl-ethyl)-2-cyclohexylmethyl-4-morpholin-4-yl-oxo-butyramideYield 69%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(R)-2-Cyclohexylmethyl-4-morpholin-4-yl-4-oxo-butyric acid (0.20 g, 0.71 mmol) was dissolved in 6 mL of DMF and cooled to 0° C. with an ice-water bath. EDC (0.18 g, 0.92 mmol) and 1-hydroxybenzotriazole (0.12 g, 0.92 mmol) were added and stirring, under argon, continued for 25 min. To the cold solution was added the HCl salt of O-benzyl-L-serineamide (0.16 g, 0.71 mmol), followed by addition of N-methylmorpholine (0.23 mL, 2.10 mmol) and stirring was continued overnight (16 h). The solution was diluted with 100 mL of EtOAc and washed with a 1.0 M solution of HCl (3×10 mL), a saturated solution of NaHCO3 (3×10 mL), water (100 mL) then with brine (100 mL). The organic layer was dried over MgSO4, filtered and concentrated by rotary evaporation to give (0.34 g, 106%) of the crude product which was chromatographed (SiO2, 2% MeOH in EtOAc) to give N-(2-Benzyloxy-1-carbamoyl-ethyl)-2-cyclohexylmethyl-4-morpholin-4-yl-oxo-butyramide (0.22 g, 69%).

Workup

  1. stirringstirring
  2. waitwas continued overnight
  3. custom(16 h)
  4. washwashed with a 1.0 M solution of HCl (3×10 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporation
  8. customto give (0.34 g, 106%) of the crude product which
  9. customwas chromatographed (SiO2, 2% MeOH in EtOAc)

Sources & evidence

ORD record
ord-f7e7e392573b4818b5548daa0d86676e
Source dataset
uspto-grants-2003_11
Patent number
US06649642B2

Reaction notes

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