Morpholine → HCID 58109613, compound

HRID 2037502Notes

Reaction equation

[CH2:1]([C@@:4]1([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](Br)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1.C(O[Na])(C)(C)C>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.C1(C)C=CC=CC=1>[CH2:1]([C@@:4]1([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3]

Participants

Conditions

Temperature: 80 °C

Procedure

A flask was charged with (R)-6-allyl-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one (400 mg, 0.96 mmol), morpholine (100 mg, 1.15 mmol) and t-BuONa (129 mg, 1.34 mmol) and Pd2(dba)3 (9 mg, 0.01 mmol) and BINAP (6 mg, 0.01 mmol) and toluene. The flask was heated to 80° C. and stirred overnight. The reaction mixture was concentrated to leave a residue, which was purified by preparative TLC to give (R)-6-allyl-6-(4-fluorophenyl)-3-((S)-1-(4-morpholinophenyl)ethyl)-1,3-oxazinan-2-one (162 mg, 0.4 mmol). LC-MS Method 3 tR=1.29, min, m/z=425; 1H NMR (CD3OD): 1.50 (m, 3H), 2.20 (m, 2H), 2.40 (m, 1H), 2.60 (m, 2H), 3.00 (m, 5H), 3.85 (m, 4H), 5.00 (m, 2H), 5.45 (m, 1H), 5.65 (m, 1H), 6.70 (m, 2H), 6.90 (m, 2H), 7.05 (m, 2H), 7.30 (m, 2H).

Workup

concentrationThe reaction mixture was concentrated
customto leave a residue, which
customwas purified by preparative TLC

Sources & evidence

ORD record: ord-c1373cd93651480da2458dc980509587
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08575156B2

Reaction notes

Loading…