Hydroxyamine hydrochloride → HCID 178513259, compound

HRID 2110113Notes

Reaction equation

HRID 2110113 reaction equation
Cl.[NH2:2][OH:3].O(C(C)(C)C)[K].[Br:10][C:11]1[O:12][C:13]([C:16]2[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][CH:17]=2)=[CH:14][CH:15]=1>CS(C)=O.O>[Br:10][C:11]1[O:12][C:13]([C:16]2[CH:21]=[CH:20][C:19]([C:22](=[NH:23])[NH:2][OH:3])=[CH:18][CH:17]=2)=[CH:14][CH:15]=1

Participants

6

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 23156952HCID 23156952, compoundHCID 178418922HCID 178418922, compound

Product 1

HCID 178513259HCID 178513259, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a chilled suspension of hydroxylamine hydrochloride (17.25 g, 0.25 mol) in DMSO (150 ml) was added portionwise KO-t-Bu (28.0 g, 0.25 mol) and the mixture was stirred under nitrogen for 30 min. 2-Bromo-5-(4-cyanophenyl)furan (17.37 g, 0.07 mol) was then added and the mixture was stirred overnight at room-temperature. The resulting solution was diluted with excess water to give 2-bromo-5-[4-(N-hydroxyamidino)phenyl]furan as an off-white solid, which was collected and washed with water. Yield: 19.45 g, 99%; mp 162-164° C. 1H NMR (DMSO-d6): 5.84 (broad s, 2H), 6.71 (d, J=3.6 Hz, 1H), 7.05 (d, J=3.6 Hz, 1H), 7.65 (d, J=8.4 Hz, 2H), 7.72 (d, J=8.4 Hz, 2H), 9.70 (s, 1H). IR (cm−1): 3475, 3369, 3209 (broad), 1639, 1482, 1341, 1017, 927, 787. The intermediate amidoxime (38.9 g, 0.138 mol) was dissolved in a mixture of DMSO (60 ml) and dioxane (300 ml) and with chilling was treated with a solution of LiOH hydrate (11.61 g, 0.277 mol) in water (60 ml). At room temperature, the resulting suspension was then treated dropwise via an addition funnel with dimethyl sulfate (26.18 g. 0.208 mol) over the course of ˜30 min. Following the addition, the mixture became slightly warm and the solids dissolved. After stirring overnight, the mixture was diluted with excess water and extracted with EtOAc. Purification of the residue by column chromatography on silica gel eluting with 10% EtOAc in hexane gave the slightly impure product, which was further purified by recrystallization from MeOH/water in multiple crops to give an off-white solid, mp 116-117° C. Yield: 28.0 g, 69%. 1H NMR (DMSO-d6, an apparent mixture of stereoisomers): 3.74 (2s, 3H), 6.09 (broad s, 2H), 6.72 (2d, J=3.6 Hz, 1H), 7.09 (2d, J=3.6 Hz, 1H), 7.70 (m, 4H). IR (cm−1): 3459, 3312, 3177, 2957, 2935, 2901, 2818, 1634, 1403, 1051, 910, 842, 785.

Workup

  1. stirringthe mixture was stirred overnight at room-temperature

Sources & evidence

ORD record
ord-790160e8b10946e9ada2ddc0b3109921
Source dataset
uspto-grants-2009_04
Patent number
US07517893B2

Reaction notes

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