Reaction #1747889

Reaction equation

DCC

NMM

HOBt

amine

3-Amino-2-tert-Butoxycarbonylamino-1-(tert-butyldimethyl-silanyloxy)butane

N-Cbz-N,O-dimethyltyrosine

→

111

Yield 70.0%

3-(N-Cbz-N,O-Dimethyltyrosyl)amino-2-tert-butoxycarbonylamino-1-(tert-butyl-dimethylsilanyloxy)butane

Yield 70.0%

Solvents

CH2Cl2

CH2Cl2

CH2Cl2

Conditions

Workup

1. 1
   workup.STIRRINGThe mixture was stirred 16 h at room temperature
2. 2
   Filtrationfiltered
3. 3
   Otherto remove the precipitate
4. 4
   workup.ADDITIONThe filtrate was diluted with CH2Cl2 (10 mL)
5. 5
   Washwashed with 10% KHSO4 (10 mL), 5% NaHCO3 (10 mL) and NaCl (10 mL, sat)
6. 6
   Dryingdried (Na2SO4)
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated
9. 9
   OtherThe crude oil was purified by column chromatography (silica gel, EtOAc/Hexanes 1/3)

Procedure

To a solution of amine 110 (20 mg, 0.062 mmol) in CH2Cl2 (1 mL), cooled to 0° C., NMM (7 μL, 0.069 mmol) and HOBt (25 mg, 0.18 mmol) were added. The solution was stirred at 0° C. for 15 minutes, and a solution of N-Cbz-N,O-dimethyltyrosine (21) (21 mg, 0.062 mmol) in CH2Cl2 (1 mL) was added. Finally a solution of DCC (14.2 mg, 0.069 mmol) in CH2Cl2 (1 mL) was added. The mixture was stirred 16 h at room temperature and filtered to remove the precipitate. The filtrate was diluted with CH2Cl2 (10 mL) and washed with 10% KHSO4 (10 mL), 5% NaHCO3 (10 mL) and NaCl (10 mL, sat), dried (Na2SO4), filtered, and concentrated. The crude oil was purified by column chromatography (silica gel, EtOAc/Hexanes 1/3) to yield 111 (26 mg, 70%) as a white foam. Rf 0.36 (AcOEt/Hexanes 1/3). [α]D20=−40.1 (c=0.5, CHCl3). 1H-NMR (500 MHz, CDCl3): 0.09 (s, 6H), 0.95 (s, 9H), 1.14-1.17 (m, 3H), 1.43 (s, 9H), 2.86 (s, 3H), 3.29-3.32 (m, 1H), 3.42-3.48 (m, 1H), 3.60-3.68 (m, 2H), 3.82 (s, 3H), 4.17-4.18 (m, 1H), 4.87-4.89 (m, 1H), 4.95-4.96 (m, 1H), 5.02-5.14 (m, 2H), 5.21-5.22 (m, 2H), 6.34-6.37 (m, 1H), 6.79-6.83 (m, 2H), 6.98-7.00 (m, 1H), 7.01-7.17 (m, 2H), 7.20-7.36 (m, 5H). 13C-NMR (125 MHz, CDCl3): −5.5, 17.9, 18.2, 25.8, 28.3, 33.2, 44.5, 55.12, 62.6, 67.3, 57.1, 66.1, 113.8, 127.5, 127.9, 128.4, 129.8, 158.2, 171.5. IR (neat) 3328.5, 2930.3, 2856.3, 2361.0, 2346.6, 2249.0, 1708.8, 1513.7, 1452.5, 1449.5. HRMS m/z cald for C34H53N5O7Na (M+Na): 666.3550 found 666.3571.

Source