Sodium borohydride → HCID 14838430, compound

HRID 1196016Notes

Reaction equation

HRID 1196016 reaction equation
[BH4-].[Na+].Cl.[CH3:4][O:5][C:6]([C:8]1[CH2:9][N:10]([CH2:15][CH2:16][CH:17]2[O:22][C:21]3[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=3[O:19][CH2:18]2)[CH2:11][CH2:12][C:13]=1[OH:14])=[O:7].Cl.COC(C1C(=O)CCN(CCC2OC3C=CC=CC=3OC2)C1)=O>CO>[CH3:4][O:5][C:6]([C@H:8]1[C@H:13]([OH:14])[CH2:12][CH2:11][N:10]([CH2:15][CH2:16][CH:17]2[O:22][C:21]3[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=3[O:19][CH2:18]2)[CH2:9]1)=[O:7]

Participants

5

Reactant 3

HCID 4311764Sodium borohydrideHCID 14838427HCID 14838427, compoundHCID 67907005HCID 67907005, compound

Product 1

HCID 14838430HCID 14838430, compoundYield 48.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

At -15° and while stirring, 2.65 g (70 mmol) of sodium borohydride are added in portions over a period of one hour to a suspension of 12.45 g (35 mmol) of 1-[2-(benzo-1,4-dioxan-2-yl)ethyl]-4-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxylic acid methyl ester hydrochloride or 1-[2-(benzo-1,4-dioxan-2-yl)ethyl]-4-oxopiperidine-3-carboxylic acid methyl ester hydrochloride, respectively, in 250 ml of methanol. Stirring is continued for a further 4 hours at -10° and then the reaction mixture is concentrated by evaporation in vacuo and taken up in water/ethyl acetate. The ethyl acetate extracts are washed with water, dried over sodium sulphate and concentrated by evaporation. 11.2 g (100%) of crude product are obtained which are chromatographed on 560 g of silica gel (0.040-0.063 mm) using ethyl acetate as the eluant. 5.41 g (48.2%) of trans-1-[2-(benzo-1,4-dioxan-2-yl)ethyl]-4-hydroxypiperidine-3-carboxylic acid methyl ester are obtained in the form of a pale yellow oil. The trans-1-[2-(benzo-1,4-dioxan-2-yl)ethyl]-4-hydroxypiperidine-3-carboxylic acid methyl ester fumarate produced therefrom using fumaric acid crystallises from methanol/diethyl ether in the form of the hemihydrate having a melting point of 150°-152°.

Workup

  1. stirringStirring
  2. concentrationthe reaction mixture is concentrated by evaporation in vacuo
  3. washThe ethyl acetate extracts are washed with water
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated by evaporation
  6. custom11.2 g (100%) of crude product are obtained which
  7. customare chromatographed on 560 g of silica gel (0.040-0.063 mm)

Sources & evidence

ORD record
ord-56bf6c970be74276acb3df7dcb0d0c4b
Source dataset
uspto-grants-1992_05
Patent number
US05112855

Reaction notes

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