Ammonium Hydroxide → 9-tert-butyl-2-bromo-3-methoxy-5,6,9,10,11,12-hexahydro-8H-azepino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8-one

HRID 1971703Notes

Reaction equation

[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:15](=O)[C:16]([N:18]([C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:19][CH2:20][CH2:21][C:22]#CC3SC=CC=3)=[O:17])[CH:9]2[C:12](O)=O)=[CH:4][C:3]=1[O:34][CH3:35].C(N(CCCC#C)C(=O)C(O)=O)(C)(C)C.C([O-])(=O)C.[Na+].[NH4+].[OH-]>C(OC(=O)C)(=O)C.O>[C:29]([N:18]1[CH2:19][CH2:20][CH2:21][C:22]2[CH:12]=[C:9]3[C:10]4[CH:11]=[C:2]([Br:1])[C:3]([O:34][CH3:35])=[CH:4][C:5]=4[CH2:6][CH2:7][N:8]3[C:15]=2[C:16]1=[O:17])([CH3:30])([CH3:31])[CH3:32]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 1 g of 13a (prepared analogously to compound 3c, starting from 2-(tert-butyl(pent-4-ynyl)amino)-2-oxoacetic acid) and 1 g of sodium acetate in 10 ml of acetic anhydride was heated at 100° C. for 1 hr. The reaction mixture was cooled and 30 ml of water was added and stirred for 1 hr to decompose excess anhydride. The reaction mixture was neutralized by addition of cold conc. NH4OH and the product was extracted with ethyl acetate. The extract was washed with water, dried, concentrated and passed through a short silica column (toluene/ethyl acetate as eluent). The product obtained was triturated with heptane, to provide 0.65 g of 13b as white crystalline material; Mp 163-165° C. MS-ESI: [M+1] 417.13 and 419.17.

Workup

temperatureThe reaction mixture was cooled
extractionthe product was extracted with ethyl acetate
washThe extract was washed with water
customdried
concentrationconcentrated
customThe product obtained
customwas triturated with heptane

Sources & evidence

ORD record: ord-394e217c701a48c5a94ae497ab829ffe
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431564B2

Reaction notes

Loading…