Reaction #89634

Reaction equation

(3R,4S)-tert-butyl 3-acetamido-3-(tert-butylcarbamoyl)-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-1-carboxylate

HCl dioxane

→

HCl

title compound

(3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide

Solvents

ether

Conditions

Workup

1. 1
   workup.STIRRINGstirred a few minutes
2. 2
   Filtrationfiltered
3. 3
   Washthe solid rinsed with ether
4. 4
   Othercollected
5. 5
   Otherdried in vacuo

Procedure

A 250 mL 3-neck round bottom flask was charged with (3R,4S)-tert-butyl 3-acetamido-3-(tert-butylcarbamoyl)-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-1-carboxylate (4.95 g, 10 mmol) and 4 N HCl/dioxane (50 mL). After stirring for 3 h the solution was diluted with ether (125 mL), stirred a few minutes, filtered, and the solid rinsed with ether, collected, and dried in vacuo to afford an HCl salt of the title compound. This was dissolved in water (30 mL) and treated with sodium hydroxide (0.5 g, 12.5 mmol). The aqueous solution was treated with sufficient potassium carbonate to render the free base product insoluble. The mixture was extracted with methylene chloride (75 mL, then 3×50 mL) and the combined organic solution was washed with saturated aqueous sodium chloride (30 mL), dried (Na2SO4), and concentrated to afford (3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide (3.40 g, 86%) as a white solid. NMR (CDCl3) δ 8.26 (br s, 1 H), 7.25 (s, 1 H), 3.86 (d, J=9.5 Hz, 1 H), 3.53 (t, J=9.5 Hz, 1 H), 3.20 (d, J=10 Hz, 1 H), 2.98 (m, 1 H), 2.74 (dd, J1=10 Hz, J2=7.5 Hz, 1 H), 2.02 (s, 3 H), 1.50 (m, 1 H), 1.33 (s, 9 H), 1.20-1.40 (m, 3 H), 1.22 (s, 12 H), 0.70-0.80 (m, 2 H). MS (m+1): 396.0.

Source