Hydrochloric Acid → tert-Butyl [1-(3-azetidin-3-yl-5-chloro-2-methoxy-4-methylphenyl)ethyl]carbamate

HRID 510936Notes

Reaction equation

HRID 510936 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:11]1[C:12]([O:33][CH3:34])=[C:13]([CH:19]2[CH2:22][N:21](C(OCC3C=CC=CC=3)=O)[CH2:20]2)[C:14]([CH3:18])=[C:15]([Cl:17])[CH:16]=1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.O>[Pd].CO>[NH:21]1[CH2:22][CH:19]([C:13]2[C:12]([O:33][CH3:34])=[C:11]([CH:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH3:10])[CH:16]=[C:15]([Cl:17])[C:14]=2[CH3:18])[CH2:20]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 86666852Benzyl 3-(3-{1-[(tert-butoxycarbonyl)amino]ethyl}-5-chloro-2-methoxy-6-methylphenyl)azetidine-1-carboxylate

Product 1

HCID 131733267tert-Butyl [1-(3-azetidin-3-yl-5-chloro-2-methoxy-4-methylphenyl)ethyl]carbamateYield 75.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Benzyl 3-(3-{1-[(tert-butoxycarbonyl)amino]ethyl}-5-chloro-2-methoxy-6-methylphenyl)azetidine-1-carboxylate (720 mg, 1.5 mmol) (second peak from chiral separation of previous step) and 5% palladium on carbon (100 mg) were combined in methanol (40 mL), to which was added 0.25 M HCl in water (11 mL, 2.8 mmol). The suspension was hydrogenated under balloon pressure of H2 at room temperature for 1 hour. The suspension was then filtered, neutralized with sat. NaHCO3 solution, concentrated, and extracted with dichloromethane. The combined organic layers were dried over MgSO4 and concentrated to give the desired product (0.4 g). LCMS calculated for C18H28ClN2O3 (M+H)+: m/z=355.2. found: 355.1.

Workup

  1. filtrationThe suspension was then filtered
  2. concentrationconcentrated
  3. extractionextracted with dichloromethane
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-b1ba3fd9c59b4fbe94825f7eee50475a
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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