Ammonia → HCID 59383359, compound

HRID 2355834Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[C:18]3[C:13](=[CH:14][C:15]([O:19][CH2:20][CH2:21][CH2:22]OS(C)(=O)=O)=[CH:16][CH:17]=3)[C@@H:12]3[CH2:28][CH2:29][CH2:30][N:11]3[CH2:10]2)=[CH:5][CH:4]=1.C([O-])([O-])=O.[Na+].[Na+].[NH:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1.N>C(O)C.C(Cl)Cl.CO.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[C:18]3[C:13](=[CH:14][C:15]([O:19][CH2:20][CH2:21][CH2:22][N:37]4[CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)=[CH:16][CH:17]=3)[C@@H:12]3[CH2:28][CH2:29][CH2:30][N:11]3[CH2:10]2)=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of crude cis-methanesulfonic acid 3-[6-(4-methoxy-phenyl)-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinolin-9-yloxy]-propyl ester (28.5 mmol), Na2CO3 (4 equiv.), KI (0.5 equiv.), and morpholine (7.52 mmol, 10 equiv.) in ethanol (0.2 M) was heated to 50° C. overnight. The mixture was cooled to rt, diluted with CH2Cl2, and filtered. The filtrate was concentrated to give the crude product. Column chromatography (NH3 in MeOH/CH2Cl2) followed by HPLC give the desired product (8.19 g, 68%). The enantiomers were separated using a Chiralcel AD-h column on a SFC HPLC eluting with IPA/MeOH with 0.2% DEA. MS: exact mass calcd for C26H34N2O3, 422.3; m/z found, 423.5 [M+H]+. 1H NMR (MeOH-d4): 7.06 (d, J=8.5, 2H), 6.82 (d, J=8.5, 2H), 6.70 (d, J=2.5, 1H), 6.67 (d, J=8.5, 1H), 6.61 (dd, J=2.5, 8.5 1H), 4.08 (dd, J=8.5, 5.5, 1H), 3.97 (t, J=6.5, 2H), 3.79 (m, 1H), 3.74 (s, 3H), 3.67 (m, 4H), 2.91 (m, 3H), 2.78 (dd, J=5.0, 11.2, 1H), 2.47 (m, 6H), 2.34 (m, 1H), 1.91 (m, 5H).

Workup

temperatureThe mixture was cooled to rt
filtrationfiltered
concentrationThe filtrate was concentrated
customto give the crude product

Sources & evidence

ORD record: ord-d56aa76fe4c34f9aa6202be11abd8688
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07754882B2

Reaction notes

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