Hydrochloric Acid → HCID 59006942, compound

HRID 1174538Notes

Reaction equation

HRID 1174538 reaction equation
Cl.[H][H].[CH2:4]([O:6][C:7]1[CH:8]=[C:9]([C@@H:15]2[C@H:20]([NH:21][C@@H](C3C=CC=CC=3)C)[CH2:19][CH2:18][O:17][CH2:16]2)[CH:10]=[CH:11][C:12]=1[O:13][CH3:14])[CH3:5]>[Pd].CO>[CH2:4]([O:6][C:7]1[CH:8]=[C:9]([C@@H:15]2[C@H:20]([NH2:21])[CH2:19][CH2:18][O:17][CH2:16]2)[CH:10]=[CH:11][C:12]=1[O:13][CH3:14])[CH3:5]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 67174522HCID 67174522, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 59006942HCID 59006942, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A suspension of 50 mmol of 3-(3-ethoxy-4-methoxy-phenyl)-tetrahydro-pyran-4-one, 75 mmol of (R)-phenylethyl amine, 5 mmol of p-toluenesulfonic acid mono-hydrate and 1 g of platin-on-carbon catalyst (3% Pt) in 400 ml of absolute methanol is hydrogenated at 60° C. and 100 mbar hydrogen pressure until no further ketone can be detected by TLC. After cooling to RT the suspension is filtered over a tonsil layer and the filtrate is concentrated under vacuum. The viscous residue is partitioned between dichloromethane and 20% citric acid solution. The pH of the aqueous phase is neutralized to about 6.0 with diluted sodium hydroxide solution and the aqueous phase is extracted 4 times with dichloromethane. The combined organic phases are dried over sodium sulfate and concentrated under vacuum yielding [(3R,4R)-3-(3-ethoxy-4-methoxy-phenyl)-tetrahydro-pyran-4-yl]-((R)-1-phenyl-ethyl)-amine as main compound. The viscous residue is not further purified and used for the next step as raw product as it is. The viscous residue is dissolved in 1.2 equivalent of 37% hydrochloric acid and methanol and palladium-on-carbon catalyst is added. The slurry is hydrogenated at 60° C. and 100 mbar hydrogen pressure until no further [(3R,4R)-3-(3-ethoxy-4-methoxy-phenyl)-tetrahydro-pyran-4-yl]-((R)-1-phenyl-ethyl)-amine can be detected by TLC. After cooling to RT the suspension is filtered over a tonsil layer and the filtrate is concentrated under vacuum. The viscous residue is purified by silica gel or aluminium oxide chromatography. The main product fraction is concentrated in vacuo and affords the title compound as solid foaming residue.

Workup

  1. customThe viscous residue is not further purified
  2. customis hydrogenated at 60° C.
  3. filtrationis filtered over a tonsil layer
  4. concentrationthe filtrate is concentrated under vacuum
  5. customThe viscous residue is purified by silica gel or aluminium oxide chromatography
  6. concentrationThe main product fraction is concentrated in vacuo

Sources & evidence

ORD record
ord-6d935ce2c2b34e3ca38644dc0b1628df
Source dataset
uspto-grants-2010_11
Patent number
US07838521B2

Reaction notes

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