Hydroxylamine → (2R)-4-[4-(4-fluorophenyl)piperazin-1-yl]-N,2-dihydroxy-4-oxobutanamide

HRID 217649Notes

Reaction equation

HRID 217649 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14](=[O:24])[CH2:15][C@H:16]3[O:20]C(C)(C)[O:18][C:17]3=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[NH2:25][OH:26]>CC(O)C.C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14](=[O:24])[CH2:15][C@@H:16]([OH:20])[C:17]([NH:25][OH:26])=[O:18])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 787HydroxylamineHCID 11709792(5R)-5-{2-[4-(4-fluorophenyl)-1-piperazinyl]-2-oxoethyl}-2,2-dimethyl-1,3-dioxolan-4-one

Product 1

HCID 11536890(2R)-4-[4-(4-fluorophenyl)piperazin-1-yl]-N,2-dihydroxy-4-oxobutanamideYield 80.3%

Reagents, catalysts & solvents 1

HCID 22597222Tetrahydrofuran 2-propanolSolvent

Procedure

To a solution of (5R)-5-{2-[4-(4-fluorophenyl)-1-piperazinyl]-2-oxoethyl}-2,2-dimethyl-1,3-dioxolan-4-one (336 mg; 1.0 mmol; 1.0 eq.) in i-PrOH/THF (25/75) (5 mL) wad added an aqueous solution of hydroxylamine (50%, 0.295 mL; 5.0 mmol; 5.0 eq.). After stirring 3 h at RT, the solvents were evaporated to give a solid. This solid was crystallized from AcOEt (by addition of Et2O and c-Hex) to give the title compound as a white powder (250 mg, 80%). M+(ESI): 312.1; M−(ESI): 310.1. 1H NMR (DMSO-d6, 300 MHz) δ 10.50 (s, 1H), 8.72 (s, 1H), 7.12-6.91 (m, 4H), 5.46 (d, J=3.0 Hz, 1H), 4.28 (q, J=6.3 Hz, 1H), 3.60 (s, 4H), 3.14-2.95 (m, 4H), 2.65 (d, J=6.3 Hz, 2H). HPLC (Condition A): Rt: 1.6 min (HPLC purity: 85.6%).

Workup

  1. customthe solvents were evaporated
  2. customto give a solid
  3. customThis solid was crystallized from AcOEt (by addition of Et2O and c-Hex)

Sources & evidence

ORD record
ord-48a3e76f09964ec18168d90e3b25ec61
Source dataset
uspto-grants-2012_06
Patent number
US08198280B2

Reaction notes

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