Hydroxylamine → HCID 58487987, compound

HRID 888234Notes

Reaction equation

HRID 888234 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][CH2:12][C@H:13]([C@@H:29]2[O:33]C(C)(C)[O:31][C:30]2=O)[C:14]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[CH2:18][CH2:17]2)=[O:15])=[CH:6][CH:5]=1)[CH3:2].[NH2:37][OH:38].CC#N>CC(O)C>[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:10][CH2:11][CH2:12][C@@H:13]([C:14]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[CH2:18][CH2:17]2)=[O:15])[C@H:29]([OH:33])[C:30]([NH:37][OH:38])=[O:31])=[CH:8][CH:9]=1)[CH3:2]

Participants

5

Reactant 3

HCID 787HydroxylamineHCID 6342AcetonitrileHCID 58487986HCID 58487986, compound

Product 1

HCID 58487987HCID 58487987, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of (5S)-5-((1R)-4-(4-ethoxyphenyl)-1-{[4-(4-fluorophenyl)-1-piperazinyl]carbonyl}butyl)-2,2-dimethyl-1,3-dioxolan-4-one (120 mg; 0.24 mmol; 1.0 eq.) in iPrOH (1 mL) was added an aq. solution of hydroxylamine (50%, 71 μl; 1.2 mmol; 5.0 eq.) and the reaction mixture was stirred for 45 min. CH3CN (4 mL) was then added and the resulting mixture was purified by chromatography by reverse-phase preparative HPLC (gradient from 25% to 45% of CH3CN containing 0.1% TFA, in water containing 0.1% TFA). The collected fractions were lyophilized to give the title compound (19) as a white solid (75 mg, 66%). 1H NMR (CDCl3, 300 MHz) δ 7.1-6.99 (m, 6H), 6.80 (d, J=8.2 Hz, 2H), 4.26 (m, 1H), 4.06 (m, 1H), 3.96 (t, 2H, J=6.8 Hz), 3.80 (m, 1H), 3.63 (m, 2H), 3.40 (m, 1H), 3.23-3.00 (m, 4H), 2.58 (m, 2H), 1.85-1.52 (m, 4H), 1.38 (t, J=6.9 Hz, 3H). M−(ESI): 472.1; M+(ESI): 474.6. HPLC: Rt: 3.2 min (HPLC purity: 93.7%).

Workup

  1. customthe resulting mixture was purified by chromatography by reverse-phase preparative HPLC (gradient from 25% to 45% of CH3CN containing 0.1% TFA, in water containing 0.1% TFA)

Sources & evidence

ORD record
ord-a6fff2418b704892be181e5276e5f202
Source dataset
uspto-grants-2012_08
Patent number
US08247437B2

Reaction notes

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