Diisopropylethylamine → (R)-tert-butyl 3,3-dimethyl-1-(methylamino)-1-oxobutan-2-ylcarbamate

HRID 1971110Notes

Reaction equation

HRID 1971110 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]([CH3:16])([CH3:15])[CH3:14])[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.CN.C[CH2:21][N:22](C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(#N)C>[CH3:14][C:13]([CH3:16])([CH3:15])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[C:10]([NH:22][CH3:21])=[O:11]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 6364545Methylamine hydrochlorideHCID 7005057(2R)-2-{[(tert-butoxy)carbonyl]amino}-3,3-dimethylbutanoic acid

Product 1

HCID 57635611(R)-tert-butyl 3,3-dimethyl-1-(methylamino)-1-oxobutan-2-ylcarbamateYield 77.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a cold solution of (R)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoic acid (0.50 g, 2.16 mmol) in acetonitrile (8 mL) was added methylamine hydrochloride (0.48 g, 7.13 mmol), followed by DIEA (1.67 g, 12.9 mmol). The resulting mixture was stirred for 20 min and TBTU (0.76 g, 2.37 mmol) was added and the stirring continued overnight. The mixture was concentrated, diluted with EtOAc (30 mL) and washed successively with aqueous 5% KHSO4, saturated NaHCO3 solution and brine, dried over anhydrous Na2SO4, filtered and concentrated to provide Intermediate 30A (0.41 g, 77%).

Workup

  1. customthe stirring continued overnight
  2. concentrationThe mixture was concentrated
  3. additiondiluted with EtOAc (30 mL)
  4. washwashed successively with aqueous 5% KHSO4, saturated NaHCO3 solution and brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-11760df5ec0a4cd9b722c20f57cf99f3
Source dataset
uspto-grants-2013_04
Patent number
US08431565B2

Reaction notes

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