Morpholine → (2R,5S)-4-Benzyl-2-methyl-5-morpholin-4-ylmethyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475503Notes

Reaction equation

C([O-])([O-])=O.[K+].[K+].[NH:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.[C:13]([O:17][C:18]([N:20]1[CH2:25][C@H:24]([CH2:26]Cl)[N:23]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:22][C@H:21]1[CH3:35])=[O:19])([CH3:16])([CH3:15])[CH3:14]>C(#N)C>[C:13]([O:17][C:18]([N:20]1[CH2:25][C@H:24]([CH2:26][N:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)[N:23]([CH2:28][C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:22][C@H:21]1[CH3:35])=[O:19])([CH3:14])([CH3:15])[CH3:16]

Participants

Conditions

Temperature: 70 °C

Procedure

K2CO3 (12.4 g, 90.0 mmol), KI (8.29 g, 51.0 mmol) and morpholine (3.9 mL, 45.0 mmol) were added to a solution of (2R,5R)-4-benzyl-5-chloromethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (10.0 g, 30.0 mmol) in acetonitrile (150 mL). The reaction was stirred at 70° C. for 18 h. The solids were filtered off and the solvent was removed in vacuo. The residue was partitioned between DCM (150 mL) and water (150 mL). The organic phase was dried (MgSO4) and evaporated. Chromatography (SiO2, eluted with petrol-EtOAc 0-50%) gave the title compound (9.0 g, 77%) as a white solid. MS: [M+H]+=390.

Workup

filtrationThe solids were filtered off
customthe solvent was removed in vacuo
customThe residue was partitioned between DCM (150 mL) and water (150 mL)
dry with materialThe organic phase was dried (MgSO4)
customevaporated
washChromatography (SiO2, eluted with petrol-EtOAc 0-50%)

Sources & evidence

ORD record: ord-6e202438177947e2ac34944553adaea1
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018214B2

Reaction notes

Loading…