Lithium hydroxide, monohydrate → 2-(Tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acid

HRID 712803Notes

Reaction equation

HRID 712803 reaction equation
[CH:1]12[CH2:6][CH:5]1[CH2:4][C@H:3]([C:7]([O:9]CC)=[O:8])[N:2]2[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].O[Li].O>O1CCOCC1.O>[C:15]([O:14][C:12]([N:2]1[CH:3]([C:7]([OH:9])=[O:8])[CH2:4][CH:5]2[CH:1]1[CH2:6]2)=[O:13])([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 58405350(3R)-2-tert-butyl 3-ethyl 2-azabicyclo[3.1.0]hexane-2,3-dicarboxylate

Product 1

HCID 213390052-(Tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acidYield 91%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of (3R)-2-tert-butyl 3-ethyl 2-azabicyclo[3.1.0]hexane-2,3-dicarboxylate (D26) (diastereoisomer mixture) (3.4 g, 13.3 mmol) in dioxane (15 ml) and water (15 ml), LiOH H2O (2.2 g, 53 mmol). The mixture was stirret at RT for 18 h. Dioxane was evaporated off and water was washed with Et2O (2×40 ml) then the pH was adjusted to ˜4 by addition of citric acid and the resulting aqueous phase was extacted with DCM (200 ml), washed with water (20 ml), dried over Na2SO4 and evaporated in vacuo to afford the title compound (D27) (2.75 g) as diastereoisomer mixture with syn-anti ratio 10/2.

Workup

  1. customDioxane was evaporated off
  2. washwater was washed with Et2O (2×40 ml)
  3. additionthe pH was adjusted to ˜4 by addition of citric acid
  4. washwashed with water (20 ml)
  5. dry with materialdried over Na2SO4
  6. customevaporated in vacuo

Sources & evidence

ORD record
ord-4408db64c5b346ab9b81bdc033596f28
Source dataset
uspto-grants-2015_11
Patent number
US09181279B2

Reaction notes

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