Benzyl chloroformate → 3-hydroxy-N-(benzyloxycarbonyl)morphinan

HRID 1924434Notes

Reaction equation

HRID 1924434 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:6][C@H:7]3[NH:18][CH2:17][CH2:16][C@@:13]4([C:14]=2[CH:15]=1)[C@H:8]3[CH2:9][CH2:10][CH2:11][CH2:12]4.[OH-].[Na+].[CH:21]1[CH:26]=[CH:25][C:24]([CH2:27][O:28][C:29](Cl)=[O:30])=[CH:23][CH:22]=1>O1CCOCC1.O>[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:6][C@H:7]3[N:18]([C:29]([O:28][CH2:27][C:24]4[CH:25]=[CH:26][CH:21]=[CH:22][CH:23]=4)=[O:30])[CH2:17][CH2:16][C@@:13]4([C:14]=2[CH:15]=1)[C@H:8]3[CH2:9][CH2:10][CH2:11][CH2:12]4

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 14798Sodium HydroxideHCID 5463854(-)-3-Hydroxymorphinan

Product 1

HCID 538511903-hydroxy-N-(benzyloxycarbonyl)morphinanYield 99.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To (+)-3-hydroxymorphinan (HM) hydrobromide (50.0 g, 154.2 mmol), sodium hydroxide (12.3 g, 308.4 mmol) in a mixture of 1,4-dioxane (200 mL) and water (200 mL) was added Cbz-Cl (24.2 mL, 169.6 mmol) dropwise at room temperature. The reaction mixture was stirred vigorously at room temperature overnight. After the reaction was completed, water (200 mL) was added. The mixture was extracted with diethyl ether (500 mL×2). The combined organics were dried over MgSO4, filtered, and evaporated under vacuum. Standing under high vacuum provided the title compound (57.7 g, 99%) as a light yellow solid. The compound was used for the next step without further purification.

Workup

  1. extractionThe mixture was extracted with diethyl ether (500 mL×2)
  2. dry with materialThe combined organics were dried over MgSO4
  3. filtrationfiltered
  4. customevaporated under vacuum

Sources & evidence

ORD record
ord-485dc268f58c480792860a5ce6a75493
Source dataset
uspto-grants-2012_05
Patent number
US08178551B2

Reaction notes

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