Hydrochloric Acid → (3S, 6R)-3-aminohexahydro-6-(cyclohexanecarbonyl)oxy-2H-azepin-2-one

HRID 1267836Notes

Reaction equation

HRID 1267836 reaction equation
C(OC([NH:8][C@H:9]1[CH2:15][CH2:14][C@@H:13]([O:16][C:17]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[O:18])[CH2:12][NH:11][C:10]1=[O:25])=O)(C)(C)C.Cl>C(OCC)(=O)C>[NH2:8][C@H:9]1[CH2:15][CH2:14][C@@H:13]([O:16][C:17]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[O:18])[CH2:12][NH:11][C:10]1=[O:25]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 11810372(3S, 6R)-3-(tert-butoxycarbonyl)aminohexahydro-6-(cyclohexanecarbonyl)oxy-2H-azepin-2-one

Product 1

HCID 11010524(3S, 6R)-3-aminohexahydro-6-(cyclohexanecarbonyl)oxy-2H-azepin-2-oneYield 114.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

(3S, 6R)-3-(tert-butoxycarbonyl)aminohexahydro-6-(cyclohexanecarbonyl)oxy-2H-azepin-2-one (300 g, 846 mmol) is added portionwise to a stirred solution of ethyl acetate (3 L) and HCl gas (225 g, 6.2 mol) at room temp. The reaction is stirred at room temp. for 6 h. The resulting precipitate is filtered and the solid is washed with ethyl acetate (1.2 L). The solid is dried to give 246 g (98%) of (3S, 6R)-3-aminohexahydro-6-(cyclohexanecarbonyl)oxy-2H-azepin-2-one.HCl which is used directly in the next step. A soln consisting of (6E)-6,7,8,9-tetradeoxy-8,8-dimethyl-2-O-methyl-3,5-O-(1-methylethylidene)-gulo-non-6-enoic acid lactone (100 g, 352 mmol), (3S, 6R)-3-aminohexahydro-6-(cyclohexanecarbonyl)oxy-2H-azepin-2-one.HCl (112.5 g, 387 mmol), sodium 2-ethylhexanoate (116 g, 700 mmol), and tetrahydrofuran (1.75 L) is stirred at room temp for 20 h. Water (350 mL) is then added to the mixture. After stirring for an additional 30 min, heptane (3.5 L) is added. The mixture is then stirred for 3 h, then cooled to 2° C. and then stirred for an additional 2 h. The mixture is filtered through a polypropylene filter. The solid that remains is washed with water (200 mL) and heptane (800 mL). The solid is then dried to give 166 g (88%) of the desired compound as a white solid.

Workup

  1. filtrationThe resulting precipitate is filtered
  2. washthe solid is washed with ethyl acetate (1.2 L)
  3. customThe solid is dried

Sources & evidence

ORD record
ord-681c39bd4a3e4952bc6277f87a08b7d1
Source dataset
uspto-grants-2003_04
Patent number
US06555533B2

Reaction notes

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