Methanesulfonyl chloride → HCID 54095088, compound

HRID 1762578Notes

Reaction equation

HRID 1762578 reaction equation
CS(Cl)(=O)=O.[CH2:6]([O:8][C:9]([CH:11]1[CH:16](O)[CH2:15][CH2:14][N:13]([CH2:18][CH:19]2[C:28]3[C:23](=[CH:24][CH:25]=[C:26]([O:29][CH3:30])[CH:27]=3)[CH2:22][CH2:21][CH2:20]2)[CH2:12]1)=[O:10])[CH3:7].N12CCCN=C1CCCCC2>C1(C)C=CC=CC=1>[CH2:6]([O:8][C:9]([C:11]1[CH2:12][N:13]([CH2:18][CH:19]2[C:28]3[C:23](=[CH:24][CH:25]=[C:26]([O:29][CH3:30])[CH:27]=3)[CH2:22][CH2:21][CH2:20]2)[CH2:14][CH2:15][CH:16]=1)=[O:10])[CH3:7]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 54450684HCID 54450684, compound

Product 1

HCID 54095088HCID 54095088, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A solution of 2.06 g (18 mmol) of methanesulphonic acid chloride in 20 ml of toluene is added dropwise, while stirring at 0°-5°, to a solution of 5.2 g (15 mmol) of cis/trans mixture of 4-hydroxy-1-[(7-methoxy-1,2,3,4-tetrahydro-naphth-1-yl)methyl]-piperidine-3-carboxylic acid ethyl ester and 11.4 g (75 mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene in 100 ml of toluene. The reaction mixture is then allowed to warm to room temperature and is stirred for a further 18 hours at room temperature. Ice-water is added to the reaction mixture and the organic phase is extracted with 2N hydrochloric acid. The combined hydrochloric acid extracts are rendered alkaline with concentrated sodium hydroxide solution and extracted with dichloromethane. The combined organic phases are washed with water, dried over sodium sulphate and concentrated by evaporation. The oily residue (4.85 g) is chromatographed on 240 g of silica gel (0.040-0.063) with toluene/ethyl acetate (9:1) to yield 1-[(7-methoxy-1,2,3,4-tetrahydro-naphth-1-yl)methyl]-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid ethyl ester in the form of a light-yellow oil. The hydrochloride produced with hydrochloric acid in diethyl ether crystallises from ethanol/diethyl ether, m.p. 177°-179° (decomposition).

Workup

  1. extractionthe organic phase is extracted with 2N hydrochloric acid
  2. extractionextracted with dichloromethane
  3. washThe combined organic phases are washed with water
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated by evaporation
  6. customThe oily residue (4.85 g) is chromatographed on 240 g of silica gel (0.040-0.063) with toluene/ethyl acetate (9:1)

Sources & evidence

ORD record
ord-b6315cbc87e3409384d6ea15d18a411a
Source dataset
uspto-grants-1989_05
Patent number
US04833169

Reaction notes

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