Morpholine → 1-(4-Morpholin-4-yl-phenyl)-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester

HRID 1400043Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[C:10]([C:14]3[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=3)([CH2:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[Na+].[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[C:10]([C:14]3[CH:19]=[CH:18][C:17]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[CH:16][CH:15]=3)([CH2:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of 1-(4-bromo-phenyl)-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (Intermediate I, 680 mg, 2.01 mmol) in anhydrous toluene (20 mL) were added Pd2(dba)3 (4.6 mg, 0.005 mmol), BINAP (9.4 mg, 0.015 mmol), sodium tert-butoxide (232 mg, 2.41 mmol) and morpholine (0.2 mL, 2.21 mmol) at r.t. and reaction mixture was stirred at 90° C. for 4 h. Reaction mixture was then concentrated and crude product was purified by column chromatography (silica gel, 1:9 EtOAc:Pet. ether) to afford the title compound as white solid (456 mg, 66%).

Workup

customreaction mixture
customReaction mixture
concentrationwas then concentrated
customcrude product was purified by column chromatography (silica gel, 1:9 EtOAc:Pet. ether)

Sources & evidence

ORD record: ord-b4196dbc4de34646825f284afb328580
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08906913B2

Reaction notes

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