1,4-Dioxane hydrochloride → Hydrochloric Acid

HRID 590700

Reaction equation

HRID 590700 reaction equation
[C:1]([NH:4][C@:5]1([C:29](=[O:35])[NH:30][C:31]([CH3:34])([CH3:33])[CH3:32])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:13]2[O:17][C:16]([CH3:19])([CH3:18])[C:15]([CH3:21])([CH3:20])[O:14]2)[CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6]1)(=[O:3])[CH3:2].[ClH:36].O1CCOCC1>CCOCC>[ClH:36].[C:1]([NH:4][C@:5]1([C:29]([NH:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:35])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:13]2[O:17][C:16]([CH3:18])([CH3:19])[C:15]([CH3:20])([CH3:21])[O:14]2)[CH2:8][NH:7][CH2:6]1)(=[O:3])[CH3:2]

Participants

5

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 67517991(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

Product 2

HCID 313Hydrochloric AcidHCID 67516451(3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

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.

Workup

  1. stirringstirred a few minutes
  2. filtrationfiltered
  3. washthe solid rinsed with ether
  4. customcollected
  5. customdried in vacuo

Sources & evidence

ORD record
ord-76fbe62983b64504be8b5ddc5f338d71
Source dataset
uspto-grants-2016_01
Patent number
US09233985B2

Linked notes

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