Hydrochloric Acid → (1S,2R,3S,4S,5R,6R)-2-Amino-3-[(3,4-dichlorobenzyl)oxy]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid hydrochloride

HRID 2173011Notes

Reaction equation

HRID 2173011 reaction equation
O.Cl.C(OC([NH:10][C@@:11]1([C:35]([O:37]C(C)(C)C)=[O:36])[C@H:16]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=2)[C@@H:15]([OH:27])[C@@H:14]2[C@H:12]1[C@H:13]2[C:28]([O:30]C(C)(C)C)=[O:29])=O)(C)(C)C>O1CCOCC1>[ClH:25].[NH2:10][C@@:11]1([C:35]([OH:37])=[O:36])[C@H:16]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=2)[C@@H:15]([OH:27])[C@@H:14]2[C@H:12]1[C@H:13]2[C:28]([OH:30])=[O:29]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962Water2×HCID 86695974Di-tert-butyl (1S,2R,3S,4S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylate

Product 1

HCID 86695987(1S,2R,3S,4S,5R,6R)-2-Amino-3-[(3,4-dichlorobenzyl)oxy]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid hydrochlorideYield 186.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of water (430 mL) and 37% HCl in water (299.9 mL, 3.65 mol) is added to a suspension of di-tert-butyl (1S,2R,3S,4S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylate (215 g, 365.3 mmol) in 1,4-dioxane (73.1 mL). The resulting slurry is stirred at 100° C. for 4.5 hours, cooled to 25° C. and concentrated in vacuo to provide a white solid. Triturate sequentially with methyl tert-butyl ether (2 L) and hexanes (2 L) and then filter to collect the solids. Dry under vacuum for 16 hours. The solid is washed again with methyl tert-butyl ether (2×1 L) and hexane (1 L), then dried under vacuum at 50° C. overnight to yield the title compound as a white solid (140.4 g, 93% yield). MS (m/z): 376/378 (M+1).

Workup

  1. temperaturecooled to 25° C.
  2. concentrationconcentrated in vacuo
  3. customto provide a white solid
  4. customTriturate sequentially with methyl tert-butyl ether (2 L) and hexanes (2 L)
  5. filtrationfilter
  6. customto collect the solids
  7. customDry under vacuum for 16 hours
  8. washThe solid is washed again with methyl tert-butyl ether (2×1 L) and hexane (1 L)
  9. customdried under vacuum at 50° C. overnight

Sources & evidence

ORD record
ord-a28f5427f1d349e7b2fbc16c997171dc
Source dataset
uspto-grants-2015_06
Patent number
US09056844B2

Reaction notes

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