Ethanol → (3aS,4R,6S,6aR)-6-(2-hydroxyethoxy)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-aminium oxalate

HRID 1045070Notes

Reaction equation

HRID 1045070 reaction equation
C(O)C.[OH:4][CH2:5][CH2:6][O:7][C@@H:8]1[C@H:12]2[O:13][C:14]([CH3:17])([CH3:16])[O:15][C@H:11]2[C@H:10]([NH2:18])[CH2:9]1.[C:19]([OH:24])(=[O:23])[C:20]([OH:22])=[O:21].C(OC(=O)C)(C)C>O>[C:19]([O-:24])(=[O:23])[C:20]([O-:22])=[O:21].[OH:4][CH2:5][CH2:6][O:7][C@@H:8]1[C@H:12]2[O:13][C:14]([CH3:16])([CH3:17])[O:15][C@H:11]2[C@H:10]([NH3+:18])[CH2:9]1.[OH:4][CH2:5][CH2:6][O:7][C@@H:8]1[C@H:12]2[O:13][C:14]([CH3:16])([CH3:17])[O:15][C@H:11]2[C@H:10]([NH3+:18])[CH2:9]1

Participants

6

Reactant 4

HCID 702EthanolHCID 971Oxalic AcidHCID 7915Isopropyl AcetateHCID 99425962-[[(3aR,4S,6R,6aS)-6-Aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol

Product 1

HCID 67288575(3aS,4R,6S,6aR)-6-(2-hydroxyethoxy)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-aminium oxalateYield 82%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
65 °C

Procedure

To an ethanol solution of (3 aS,4R,6S,6aR)-6-(2-hydroxyethoxy)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-amine (approximately 100 kg in approximately 320 kg of to ethanol, prepared as described in WO01/92263) water (30 kg) was charged. The mixture was heated to 65° C. and oxalic acid×2H2O (57 kg) was added. Iso-propylacetate (665 kg) was added during 2 hours and the resulting slurry was cooled to 20° C. in 2 hours. The cooled slurry was kept at this temperature for additionally 2 hours. The precipitated product was isolated, washed with iso-propylacetate (141 kg) and dried under vacuum to give the title compound as a white solid (116 kg, approximately 82%). 1H NMR (400 MHz, DMSO-d6) δ 6.51 (app br s, NH2, COOH and OH protons), 4.70 (app d, J=6 Hz, 1H), 4.61 (app d, J=6 Hz, 1H), 3.91 (app br s, 1H), 3.40-3.59 (m, 5H), 2.12-2.23 (m, 1H), 1.89-2.01 (m, 1H), 1.36 (s, 3H), 1.23 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 164.7, 110.8, 82.8, 82.7, 82.1, 70.5, 60.0, 55.1, 32.5, 26.1, 23.9.

Workup

  1. temperaturethe resulting slurry was cooled to 20° C. in 2 hours
  2. customThe precipitated product was isolated
  3. washwashed with iso-propylacetate (141 kg)
  4. customdried under vacuum

Sources & evidence

ORD record
ord-55f73b98152d4368ae8e026deb40888d
Source dataset
uspto-grants-2013_10
Patent number
US08563755B2

Reaction notes

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