1,2-Dichloroethane → (R)-2-Cyclohexylmethyl-4-morpholin-4-yl-4-oxo-butyric acid 1-methyl ester

HRID 480227Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:16])[C@H:4]([CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)[CH2:5][C:6]([OH:8])=O.C(Cl)CCl.ON1C2C=CC=CC=2N=N1.[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1>CN(C=O)C.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:16])[C@H:4]([CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)[CH2:5][C:6]([N:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1)=[O:8]

Participants

Conditions

Temperature: 0 °C

Procedure

(R)-2-(Cyclohexylmethyl) succinic acid 1-methyl ester (1.00 g, 4.38 mmol) was dissolved in 10 mL of DMF and cooled to 0° C. with an ice-water bath. EDC (1.12 g, 5.69 mmol) then 1-hydroxybenzotriazole (0.77 g, 5.69 mmol) were added and stirring continued, under argon, for 25 min. Morpholine (0.76 mL, 8.76 mmol) was added and stirring was continued overnight (16 h). The solution was diluted with 200 mL of EtOAc and washed with a 1.0 M solution of HCl (3×100 mL), a saturated solution of NaHCO3 (3×100 mL), water (100 mL), then with brine (100 mL). The organic layer was dried over MgSO4, filtered and concentrated by rotary evaporation to give (R)-2-Cyclohexylmethyl-4-morpholin-4-yl-4-oxo-butyric acid 1-methyl ester (1.26 g, 99%) as a white solid. The product was used in the following step without purification.

Workup

stirringstirring
waitwas continued overnight
custom(16 h)
washwashed with a 1.0 M solution of HCl (3×100 mL)
dry with materialThe organic layer was dried over MgSO4
filtrationfiltered
concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record: ord-865e4d1382e145e787c14a0ae3a8e738
Source dataset: uspto-grants-2003_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06649642B2

Reaction notes

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