Lithium Bromide → Cabotegravir

HRID 2273027Notes

Reaction equation

[Li+].[Br-].[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[CH2:11][NH:12][C:13]([C:15]1[C:16](=[O:32])[C:17]([O:30]C)=[C:18]2[C:23](=[O:24])[N:22]3[C@@H:25]([CH3:28])[CH2:26][O:27][C@@H:21]3[CH2:20][N:19]2[CH:29]=1)=[O:14]>C1COCC1>[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[CH2:11][NH:12][C:13]([C:15]1[C:16](=[O:32])[C:17]([OH:30])=[C:18]2[C:23](=[O:24])[N:22]3[C@@H:25]([CH3:28])[CH2:26][O:27][C@@H:21]3[CH2:20][N:19]2[CH:29]=1)=[O:14]

Participants

Conditions

Temperature: 20 °C

Procedure

Alternatively, the demethylation can be carried out with LiBr: (3S,11aR)—N-[(2,4-Difluorophenyl)methyl]-3-methyl-6-(methyloxy)-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide (8.609 g) was dissolved in THF (90 mL) and LiBr (3.942 g) was added. The mixture was heated to reflux for 12 h and quenched with H2SO4 (0.5 M, 94.467 g). The resultant suspension was stirred at 20° C. for 2 h and filtered. The solid product was re-slurried in water-THF (50 mL-50 mL) at 20° C. for 2 h. The product was collected by filtration, rinsed with water-THF (1-1, 30 mL), and dried under vacuum to afford the product.

Workup

temperatureThe mixture was heated
temperatureto reflux for 12 h
customquenched with H2SO4 (0.5 M, 94.467 g)
filtrationfiltered
waitThe solid product was re-slurried in water-THF (50 mL-50 mL) at 20° C. for 2 h
filtrationThe product was collected by filtration
washrinsed with water-THF (1-1, 30 mL)
customdried under vacuum
customto afford the product

Sources & evidence

ORD record: ord-74a565e545934c38be4ddd1ec4f5cb1b
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09120817B2

Reaction notes

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