Diisopropylethylamine → Boc-Asp(OBzl)-NHMe

HRID 1160399Notes

Reaction equation

HRID 1160399 reaction equation
[CH:1]([N:4](CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:34][C:35]([O:38][C:39]([NH:41][C@H:42]([C:54]([OH:56])=O)[CH2:43][C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45])=[O:40])([CH3:37])[CH3:36].Cl.CN>CC(N(C)C)=O.C(Cl)Cl>[CH3:34][C:35]([O:38][C:39]([NH:41][C@H:42]([C:54](=[O:56])[NH:4][CH3:1])[CH2:43][C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45])=[O:40])([CH3:37])[CH3:36]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1581888N-tert-Butoxycarbonyl-L-aspartic acid beta-benzyl esterHCID 6364545Methylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 59516205Boc-Asp(OBzl)-NHMeYield 78.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent

Procedure

N,N-Diisopropylethylamine (15.10 g, 116.8 mmol) and HATU (10.77 g, 28.34 mmol) were added to a suspension of Boc-Asp-(OBzl)-OH (7.61 g, 23.54 mmol) and methylamine hydrochloride (5.03 g, 74.50 mmol) in DMA (31 mL). After stirring at room temperature for 18 h, the reaction mixture was diluted with CH2Cl2 and washed with saturated NaHCO3. The organic layer was washed with H2O several times, dried over Na2SO4, filtered, and concentrated. The residue was purified via silica gel chromatography with 0% MeOH in CH2Cl2 grading to 4% MeOH in CH2Cl2 to afford the titled product (6.2 g, 78%) as a white solid. 1H-NMR (CDCl3) δ: 1.471 (9H, s), 2.730 (1H, m), 2.818 (3H, d, J=4.8 Hz), 3.120 (1H, m), 4.520 (1H, s), 5.156 (2H, m), 5.660 (1H, s), 6.430 (1H, s), 7.378 (5H, m). LC-MS (ES) m/e 337.2 (M+H)+.

Workup

  1. washwashed with saturated NaHCO3
  2. washThe organic layer was washed with H2O several times
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified via silica gel chromatography with 0% MeOH in CH2Cl2 grading to 4% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-9dfe901d3ae04917b738f55545094cb1
Source dataset
uspto-grants-2010_10
Patent number
US07816395B2

Reaction notes

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