Methanamine, N-methoxy-, hydrochloride (1:1) → N-methoxy-N-methyl-(R)-5-(benzyloxycarbonylamino)-2-(tert-butoxycarbonylamino)pentanamide

HRID 1050555Notes

Reaction equation

HRID 1050555 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][CH2:14][C@@H:15]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C:16]([OH:18])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:28][O:29][NH:30][CH3:31].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CC#N>[CH3:28][O:29][N:30]([CH3:31])[C:16](=[O:18])[C@H:15]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:14][CH2:13][CH2:12][NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10]

Participants

6

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 7272030N2-((1,1-Dimethylethoxy)carbonyl)-N5-((phenylmethoxy)carbonyl)-D-ornithine

Product 1

HCID 118114437N-methoxy-N-methyl-(R)-5-(benzyloxycarbonylamino)-2-(tert-butoxycarbonylamino)pentanamideYield 99%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a 1-liter round bottom flask were added (R)-5-(benzyloxycarbonylamino)-2-(tert-butoxycarbonylamino)pentanoic acid (10 g, 27 mmol), N-methoxy-N-methylamine-HCl (5.3 g, 55 mmol), PyBOP (21 g, 41 mmol), and MeCN (400 mL). DIEA (19 mL, 110 mmol) was added and the reaction was allowed to stir at room temperature for 12 hours. The solvent was removed under reduced pressure and the residue was suspended in EtOAc and washed with 1N NaOH (aq) (×3) then 2N HCl (aq) (×2), then saturated NaHCO3 (aq) (×1), then brine (×1). The product was then purified by column chromatography (EtOAc/hexanes) to give N-methoxy-N-methyl-(R)-5-(benzyloxycarbonylamino)-2-(tert-butoxycarbonylamino)pentanamide (305) (10.9 g, 26.7 mmol, 99% yield) as a clear oil.

Workup

  1. customThe solvent was removed under reduced pressure
  2. washwashed with 1N NaOH (aq) (×3)
  3. customThe product was then purified by column chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-7efec06820764ba5857a7190c11244ad
Source dataset
uspto-grants-2016_07
Patent number
US09382246B2

Reaction notes

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