Hydrochloric Acid → HCID 44592086, compound

HRID 2384597Notes

Reaction equation

HRID 2384597 reaction equation
[CH:1]1([CH2:4][N:5]2[CH2:25][CH2:24][C@:12]34[C:13]5[C:14]6[O:23][C@H:11]3[C:10](=O)[CH2:9][CH2:8][C@@:7]4([OH:27])[C@H:6]2[CH2:19][C:18]=5[CH:17]=[CH:16][C:15]=6[C:20]([NH2:22])=[O:21])[CH2:3][CH2:2]1.Cl>C(O)(=O)C.[Zn]>[CH:1]1([CH2:4][N:5]2[CH2:25][CH2:24][C@@:12]34[C:13]5[C:14]([OH:23])=[C:15]([C:20]([NH2:22])=[O:21])[CH:16]=[CH:17][C:18]=5[CH2:19][C@@H:6]2[C@:7]3([OH:27])[CH2:8][CH2:9][CH2:10][CH2:11]4)[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 10021946Samidorphan

Product 1

HCID 44592086HCID 44592086, compoundYield 29.4%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
125 °C

Procedure

To a mixture of (5a)-17-(cyclopropylmethyl)-14-hydroxy-6-oxo-4,5-epoxymorphinan-3-carboxamide [P3] (3.74 g, 10.2 mmol) and zinc powder (33.0 g, 0.51 mol) in acetic acid (220 mL) was added 12N HCl (30 mL). The reaction was heated at 125° C. for 3 hours then allowed to return to room temperature. The mixture was slowly quenched into an ice/water cooled ammonium hydroxide solution at such a rate to ensure the temperature remained below 20° C. The resultant suspension was extracted with DCM (3×500 mL) and dried (MgSO4). Filtration and removal of the solvent under reduced pressure gave the crude product that was purified by prep-HPLC [Xbridge Prep C18 OBD, 30×150 mm, 5 μm; Mobile Phase A: 10 mM NH4HCO3 (pH 10), Phase B: MeCN; Flow: 50 ml/min; Column Temperature: 30° C.; Runtime: 25 min.] giving 17-(cyclopropylmethyl)-4,14-dihydroxymorphinan-3-carboxamide [13] (1.07 g, 29% yield); LC/MS (r.t. 10.2 minutes [5 to 95% B]), 357 (M+H)+.

Workup

  1. customto return to room temperature
  2. customThe mixture was slowly quenched into an ice/water
  3. temperaturecooled ammonium hydroxide solution at such a rate
  4. customremained below 20° C
  5. extractionThe resultant suspension was extracted with DCM (3×500 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationFiltration and removal of the solvent under reduced pressure
  8. customgave the crude product that
  9. customwas purified by prep-HPLC [Xbridge Prep C18 OBD, 30×150 mm, 5 μm; Mobile Phase A: 10 mM NH4HCO3 (pH 10), Phase B: MeCN; Flow: 50 ml/min; Column Temperature: 30° C.; Runtime: 25 min.]

Sources & evidence

ORD record
ord-3f7836fe2db245da80e6502e9d5b5b7f
Source dataset
uspto-grants-2012_09
Patent number
US08263807B2

Reaction notes

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