Aniline → Hydrochloric Acid

HRID 1508287Notes

Reaction equation

[CH:1]1([CH2:4][N:5]2[CH2:14][CH2:13][C@@:12]34[C:15]5[C:21]6[CH2:22][C@@H:6]2[C@@:7]23[CH2:25][CH2:24][C@:10]([O:26][CH3:27])([C@@H:11]4[O:17][C:16]=5[C:18]([OH:23])=[CH:19][CH:20]=6)[C@@H:9]([CH2:28][O:29][CH2:30][C:31]3[CH:32]=[C:33]([NH:37][C:38](=[O:40])[CH3:39])[CH:34]=[CH:35][CH:36]=3)[CH2:8]2)[CH2:3][CH2:2]1.BrC1C=C(C=CC=1)CBr.NC1C=CC=CC=1.C([Cl:60])(=O)C.C(O)(C(F)(F)F)=O>>[CH:1]1([CH2:4][N:5]2[CH2:14][CH2:13][C@@:12]34[C:15]5[C:21]6[CH2:22][C@@H:6]2[C@@:7]23[CH2:25][CH2:24][C@:10]([O:26][CH3:27])([C@@H:11]4[O:17][C:16]=5[C:18]([OH:23])=[CH:19][CH:20]=6)[C@@H:9]([CH2:28][O:29][CH2:30][C:31]3[CH:32]=[C:33]([NH:37][C:38](=[O:40])[CH3:39])[CH:34]=[CH:35][CH:36]=3)[CH2:8]2)[CH2:2][CH2:3]1.[ClH:60]

Participants

Reactant 5

HCID 6115Aniline2×

HCID 6367Acetyl chloride

HCID 6422Trifluoroacetic acid

HCID 699793-Bromobenzyl bromide

HCID 66826663HCID 66826663, compound2×

Product 2

HCID 313Hydrochloric Acid

HCID 66826663HCID 66826663, compound

Procedure

In a similar manner N-(3-((((4R,4aS,6R,7R,7aR,12bS)-3-(cyclopropylmethyl)-9-hydroxy-7-methoxy-1,2,3,4,5,6,7,7a-octahydro-4a,7-ethano-4,12-methanobenzofuro[3,2-e]isoquinolin-6-yl)methoxy)methyl)phenyl)acetamide (Compound 72) was prepared from R-101 using 3-bromobenzyl bromide, followed by conversion of the aryl bromide to the aniline, subsequent reaction of the aniline with acetyl chloride and final cleavage of the p-methoxybenzyl group by TFA. Purification by flash column chromatography (silica gel, 0-10% MeOH/DCM) followed by HCl salt formation gave Compound 72 HCl salt as a white solid.

Workup

customPurification by flash column chromatography (silica gel, 0-10% MeOH/DCM)

Sources & evidence

ORD record: ord-0941c1880ace4f5facd328eec2ab4b70
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221831B2

Reaction notes

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