N,O-Dimethylhydroxylamine → (S)-N-methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide

HRID 575864Notes

Reaction equation

HRID 575864 reaction equation
[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7]([OH:9])=O)[CH2:3][CH:4]([CH3:6])[CH3:5].F[B-](F)(F)F.[N:22]1([O:31][C:32](N(C)C)=[N+](C)C)[C:26]2C=CC=CC=2N=N1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CNOC>C(Cl)Cl>[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7]([N:22]([CH3:26])[O:31][CH3:32])=[O:9])[CH2:3][CH:4]([CH3:5])[CH3:6]

Participants

7

Reactant 5

HCID 14232N,O-DimethylhydroxylamineHCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2×HCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate

Product 1

HCID 11119284(S)-N-methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Boc-Leu-OH (1 g, 4.3 mmol) was dissolved in DCM (30 mL) and 2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU)(1.380 g, 4.3 mmol), HOBt (0.581 g, 4.3 mmol) and DIPEA (743 μL, 4.3 mmol) were added at 0° C. After 5 min of stirring, 0,N-dimethylhydroxylamine hydrochloride (0.461 g, 4.73 mmol) and DIPEA (817 μL, 4.73 mmol) were added. All solid material dissolved within 10 min and the mixture was stirred overnight at RT. The solvent was evaporated, the reaction mixture redissolved in AcOEt and washed with H2O, 5% citric acid, H2O, 5% aqueous NaHCO3 solution, saturated NaCl solution several times. The solution was dried over MgSO4 and the solvent removed in vacuo. The desired compound was purified by silica gel column chromatography. ESI-MS: calcd. 269. found 292 [M+Na]+.

Workup

  1. dissolutionAll solid material dissolved within 10 min
  2. stirringthe mixture was stirred overnight at RT
  3. customThe solvent was evaporated
  4. dissolutionthe reaction mixture redissolved in AcOEt
  5. washwashed with H2O, 5% citric acid, H2O, 5% aqueous NaHCO3 solution, saturated NaCl solution several times
  6. dry with materialThe solution was dried over MgSO4
  7. customthe solvent removed in vacuo
  8. customThe desired compound was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a5b1eb7180c241fbb225b03966dccca8
Source dataset
uspto-grants-2015_05
Patent number
US09035023B2

Reaction notes

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