Hydroxylamine → HCID 11660575, compound

HRID 1677785Notes

Reaction equation

HRID 1677785 reaction equation
CC1(C)[O:6][C:5](=O)[C@H:4]([C@H:8]([C:13]([N:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[CH2:17][C@H:16]2[CH3:27])=[O:14])[CH2:9][CH:10]([CH3:12])[CH3:11])[O:3]1.[NH2:29][OH:30]>CC(O)C.O>[OH:30][NH:29][C:5](=[O:6])[C@@H:4]([OH:3])[C@@H:8]([C:13]([N:15]1[CH2:20][CH2:19][N:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)[CH2:17][C@H:16]1[CH3:27])=[O:14])[CH2:9][CH:10]([CH3:12])[CH3:11]

Participants

5

Reactant 2

HCID 787HydroxylamineHCID 67331938(5S)-2,2-dimethyl-5-((1R)-3-methyl-1-{[(2R)-2-methyl-4-(2-pyridinyl)piperazinyl]carbonyl}butyl)-1,3-dioxolan-4-one

Product 1

HCID 11660575HCID 11660575, compoundYield 47.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

To a solution of (5S)-2,2-dimethyl-5-((1R)-3-methyl-1-{[(2R)-2-methyl-4-(2-pyridinyl)piperazinyl]carbonyl}butyl)-1,3-dioxolan-4-one (517 mg; 1.33 mmol; 1.0 eq) in iPrOH (2.0 mL) was added an aqueous solution of hydroxylamine (391.5 μl; 6.64 mmol; 5.0 eq.) and the resulting reaction mixture was stirred at RT for 40 min. HPLC analyses showed the presence of 2 diastereoisomers (75/25). This reaction mixture was dissolved in water (6 mL) and directly purified by reverse-phase chromatography (major diastereoisomer as the first eluted peak, gradient starting from 100% H2O up to 75% H2O in ACN in 5 min, then isocratic 75% H2O in ACN for 25 min; flow: 50 mL/min) to give the title product (4) as a white powder (230 mg; 47%). 1H NMR (CD3OD, 300 MHz) δ 8.10 (m, 1H), 7.58 (m, 1H), 6.84 (m, 1H), 6.69 (m, 1H), 4.84-4.70 (m, 1H), 4.60 (m, 1H), 4.48 (m, 0.4H), 4.19 (m, 1H), 4.13-3.98 (m, 2H), 3.71-3.55 (m, 0.6H), 3.30-3.07 (m, 2H), 3.05-2.82 (m, 1H), 1.94-1.76 (m, 1H), 1.55-1.38 (m, 3H), 1.35 (d, 1.3H, J=6.7 Hz), 1.23 (d, 1.7H, J=6.7 Hz), 0.93 (m, 6H). M+(ESI): 365.2, M−(ESI): 363.2. HPLC (Condition B), Rt: 2.4 min (HPLC purity: 97.6

Workup

  1. customthe resulting reaction mixture
  2. customdirectly purified by reverse-phase chromatography (major diastereoisomer as the first eluted peak
  3. waitgradient starting from 100% H2O up to 75% H2O in ACN in 5 min
  4. waitisocratic 75% H2O in ACN for 25 min

Sources & evidence

ORD record
ord-952581214d7c470fa00f4aecb1ff3445
Source dataset
uspto-grants-2011_08
Patent number
US08008302B2

Reaction notes

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