Hydroxyamine hydrochloride → ethyl 2-[(3S)-1-[(2R)-2-hydroxy-2-[4-[(Z)-N'-hydroxycarbamimidoyl]phenyl]ethyl]piperidin-3-yl]acetate

HRID 1948497Notes

Reaction equation

[Si]([O:8][C@@H:9]([C:23]1[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][CH:24]=1)[CH2:10][N:11]1[CH2:16][CH2:15][CH2:14][C@H:13]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:12]1)(C(C)(C)C)(C)C.C(=O)(O)[O-].[Na+].Cl.[NH2:37][OH:38]>CC(O)C.C(OCC)(=O)C>[OH:8][C@H:9]([C:23]1[CH:24]=[CH:25][C:26](/[C:29](=[N:37]/[OH:38])/[NH2:30])=[CH:27][CH:28]=1)[CH2:10][N:11]1[CH2:16][CH2:15][CH2:14][C@@H:13]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:12]1

Participants

Conditions

Temperature: 75 °C

Procedure

To a mixture of ethyl 2-((R)-1-((S)-2-(tert-butyldimethylsilyloxy)-2-(4-cyanophenyl)ethyl)piperidin-3-yl)acetate (940 mg, 2.183 mmol) and sodium bicarbonate (733 mg, 8.73 mmol) in 2-propanol (50 mL) was added hydroxylamine hydrochloride (303 mg, 4.37 mmol). The reaction mixture was heated at 75° C. overnight. The reaction mixture was diluted with ethyl acetate and washed with saturated NaCl. The organic layer was dried MgSO4, filtered, and concentrated to yield 920 mg of ethyl 2-((S)-1-((R)-2-hydroxy-2-(4-((Z)—N′-hydroxycarbamimidoyl)phenyl)ethyl)piperidin-3-yl)acetate. (M+H)=464; HPLC RT=1.57 minutes. 1H NMR (400 MHz, CDCl3) δ ppm 9.48 (1H, s), 7.55 (2H, d), 7.24 (2H, d), 5.68 (1H, s), 4.74 (1H, m), 4.00 (2H, q), 2.73 (1H, m), 2.65 (1H, m), 2.38 (1H, dd), 2.20 (1H, dd), 2.13 (2H, t), 2.00 (1H, m), 1.80 (3H, m), 1.58 (1H, m), 1.48 (1H, m), 1.38 (1H, m), 1.13 (3H, t), 1.0 (1H, m), 0.85 (9H, s), 0.00 (3H, s), −0.15 (3H, s).

Workup

washwashed with saturated NaCl
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-992841a8c3e64e2a98fca0746a389d7f
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399451B2

Reaction notes

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