3,4-dihydro-2H-pyran → HCID 78139891, compound

HRID 717897Notes

Reaction equation

HRID 717897 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][CH:15]=1)[O:5][C:6]1[CH:12]=[CH:11][C:9]([NH2:10])=[CH:8][CH:7]=1.[CH:16]1([CH:22]=O)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.[O:24]1[CH:29]=[CH:28][CH2:27][CH2:26][CH2:25]1>CC#N>[Cl:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][CH:15]=1)[O:5][C:6]1[CH:12]=[CH:11][C:9]2[NH:10][CH:22]([CH:16]3[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]3)[CH:26]3[CH2:27][CH2:28][CH2:29][O:24][CH:25]3[C:8]=2[CH:7]=1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 16275CyclohexanecarboxaldehydeHCID 41972Benzenamine, 4-(3-chlorophenoxy)-

Product 1

HCID 78139891HCID 78139891, compoundYield 34.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-(3-chlorophenoxy)aniline (220 mg, 1 mmol, 1 equiv.) in dry MeCN (3 mL) under argon atmosphere was added cyclohexanecarbaldehyde (121 μL, 1 mmol, 1 equiv.) and 3,4-dihydro-2H-pyran (90 μL, 1 mmol, 1 equiv.) sequentially, followed by Mg(ClO4)2 (12.3 mg, 0.05 mmol, 0.05 equiv.). The reaction mixture was stirred at r.t. overnight. The solvent was removed under reduced pressure and the residue taken up in CH2Cl2 and passed through Decalite. The solvent of the filtrate was removed under reduced pressure and the crude crystallized from AcOEt to afford pure cis diastereomer (4aSR*,5RS*,10bSR*)-9-(3-chlorophenoxy)-5-cyclohexyl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinoline (138 mg, 34%) as white solid. The solvent from the mother liquid was evaporated and the remaining residue purified by Combiflash chromatography (SiO2, c-Hexane/AcOEt up to 10%) to obtain additionally 144 mg of the cis diastereomer (overall yield cis 71%) along with the 78 mg of trans diastereomer (4aSR*,5SR*,10bSR*)-9-(3-chlorophenoxy)-5-cyclohexyl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c] (18%) as yellow oil. The corresponding hydrochloride salts of the cis and trans diastereomer were prepared as follows.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customThe solvent of the filtrate was removed under reduced pressure
  3. customthe crude crystallized from AcOEt

Sources & evidence

ORD record
ord-ba7018ea20904167842d2a6d8e6531a5
Source dataset
uspto-grants-2015_11
Patent number
US09193738B2

Reaction notes

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