Hydroxylamine → Ethyl 2-({3-[amino(hydroxyimino)methyl]-5-fluorobenzyl}amino)-4-methylpentanoate

HRID 572551Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5]([CH:20]=[C:21]([F:23])[CH:22]=1)[CH2:6][NH:7][CH:8]([CH2:16][CH:17]([CH3:19])[CH3:18])[C:9]([O:11][C:12](C)(C)[CH3:13])=[O:10])#[N:2].[NH2:24][OH:25]>C(O)C.O>[NH2:2][C:1](=[N:24][OH:25])[C:3]1[CH:4]=[C:5]([CH:20]=[C:21]([F:23])[CH:22]=1)[CH2:6][NH:7][CH:8]([CH2:16][CH:17]([CH3:18])[CH3:19])[C:9]([O:11][CH2:12][CH3:13])=[O:10]

Participants

Conditions

Temperature: 0 °C

Procedure

To tert-butyl 2-[(3-cyano-5-fluorobenzyl)amino]-4-methylpentanoate (3.0 g, 9.4 mmol) in ethanol (30 mL) was added hydroxylamine (1.2 mL, 0.019 mol) and it was stirred at 0° C. for 16 hrs. The reaction mixture was diluted with water (250 mL) and extracted with ethyl acetate. The organic layer was separated, washed with brine, dried and concentrated. The crude product was purified by chromatography using petroleum ether/ethyl acetate as eluent, affording the title compound as a white solid (2.3 g, 70%). 1H NMR (DMSO-d6, 400 MHz): δ 9.73 (s, 1H), 7.46 (s, 1H), 7.30 (d, J=9.6 Hz, 1H), 7.13 (d, J=9.6 Hz, 1H), 5.84 (s, 2H), 3.75 (d, 1H), 3.55 (d, 1H), 2.98 (s, 1H), 2.38 (brs, 1H), 1.76-1.69 (m, 1H), 1.40 (s, 9H), 1.37 (dd, 2H), 0.96 (d, 3H), 0.87 (d, 3H). LC/MS (Method B) 354.3 (M+H)+. HPLC (Method A) Rt: 2.96 min (Purity 98.3%).

Workup

extractionextracted with ethyl acetate
customThe organic layer was separated
washwashed with brine
customdried
concentrationconcentrated
customThe crude product was purified by chromatography

Sources & evidence

ORD record: ord-08c0b770ae7144b5a91bea037b029e70
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09029405B2

Reaction notes

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