Methanesulfonic Acid → 2-Benzyl-8-(4-p-Fluorophenyl-1-Methylbutyl)-10-Hydroxy-5-Oxo-1,2,3,4-Tetrahydro-5H-[1]Benzopyrano[4,3-c]Pyridin-10-ol Hydrochloride

HRID 1580169Notes

Reaction equation

HRID 1580169 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]([CH2:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[CH3:10])[CH:5]=[C:6]([OH:8])[CH:7]=1.CS(O)(=O)=O.Cl.[CH2:27]([N:34]1[CH2:39][CH2:38][CH:37]([C:40](OCC)=[O:41])[C:36](=O)[CH2:35]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[O:46]=P(Cl)(Cl)[Cl:48].[OH-].[Na+]>C(Cl)(Cl)Cl.O>[ClH:48].[CH2:27]([N:34]1[CH2:39][CH2:38][CH:37]2[C:40](=[O:41])[O:8][C:6]3[C:7]([C:2]([OH:46])([OH:1])[CH:3]=[C:4]([CH:9]([CH3:10])[CH2:11][CH2:12][CH2:13][C:14]4[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=4)[CH:5]=3)=[C:36]2[CH2:35]1)[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

8

Reactant 5

HCID 6395Methanesulfonic AcidHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 2723880Ethyl 1-benzyl-3-oxopiperidine-4-carboxylate hydrochlorideHCID 202879045-[5-(4-Fluorophenyl)pentan-2-yl]benzene-1,3-diol

Product 1

HCID 867329212-Benzyl-8-(4-p-Fluorophenyl-1-Methylbutyl)-10-Hydroxy-5-Oxo-1,2,3,4-Tetrahydro-5H-[1]Benzopyrano[4,3-c]Pyridin-10-ol Hydrochloride

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

To 45 g. of 2-(3,5-dihydroxyphenyl)-5-(4-fluorophenyl)pentane dissolved in 100 ml. of methanesulfonic acid were added in portions, 57 g. of 1-benzyl-3-keto-4-carbethoxy piperidine hydrochloride. While stirring, 68 g. of POCl3 was added and the solution was stirred for 5 days at room temperature. Water (300 ml.) and 180 ml. of CHCl3 were then added and the reaction mixture stirred for 30 minutes. After the addition of 100 ml. of 15% NaOH, the reaction was stirred for an additional 10 minutes. The CHCl3 layer was separated and extracted with 10% HCl. The CHCl3 layer was concentrated and CH3CN added thereto to yield 55 g. of the desired product as the hydrochloride salt, m.p. 254° - 256° C.

Workup

  1. stirringthe solution was stirred for 5 days at room temperature
  2. stirringthe reaction mixture stirred for 30 minutes
  3. additionAfter the addition of 100 ml
  4. customThe CHCl3 layer was separated
  5. extractionextracted with 10% HCl
  6. concentrationThe CHCl3 layer was concentrated
  7. additionCH3CN added
  8. customto yield 55 g

Sources & evidence

ORD record
ord-5c9d7efae57643c28c5589329b0ba54b
Source dataset
uspto-grants-1976_01
Patent number
US03932432

Reaction notes

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