Diethanolamine → 4-{[4-(2-Butynyloxy)phenyl]sulfonyl}-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-piperidine-4-carboxylic acid ethylester

HRID 278327Notes

Reaction equation

HRID 278327 reaction equation
N(CCO)CCO.N1(CCOC2C=CC(CCl)=CC=2)CCCCC1.S(Cl)(Cl)=O.[CH2:29]([O:31][C:32](=[O:48])[CH2:33][S:34]([C:37]1[CH:42]=[CH:41][C:40]([O:43][CH2:44][C:45]#[C:46][CH3:47])=[CH:39][CH:38]=1)(=[O:36])=[O:35])[CH3:30].Cl.Cl.Cl[CH2:52][CH2:53][N:54]([CH2:71][CH2:72]Cl)[CH2:55][C:56]1[CH:61]=[CH:60][C:59]([O:62][CH2:63][CH2:64][N:65]2[CH2:70][CH2:69][CH2:68][CH2:67][CH2:66]2)=[CH:58][CH:57]=1>CC(C)=O>[CH2:29]([O:31][C:32]([C:33]1([S:34]([C:37]2[CH:38]=[CH:39][C:40]([O:43][CH2:44][C:45]#[C:46][CH3:47])=[CH:41][CH:42]=2)(=[O:35])=[O:36])[CH2:72][CH2:71][N:54]([CH2:55][C:56]2[CH:61]=[CH:60][C:59]([O:62][CH2:63][CH2:64][N:65]3[CH2:70][CH2:69][CH2:68][CH2:67][CH2:66]3)=[CH:58][CH:57]=2)[CH2:53][CH2:52]1)=[O:48])[CH3:30]

Participants

7

Reactant 5

HCID 8113DiethanolamineHCID 24386Thionyl ChlorideHCID 98607864-(2-Piperidin-1-yl-ethoxy)benzyl chlorideHCID 11335441Ethyl{[4-(2-butynyloxy)phenyl]sulfonyl}acetateHCID 23513818Bis-(2-chloro-ethyl)-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-amine dihydrochloride

Product 1

HCID 543555534-{[4-(2-Butynyloxy)phenyl]sulfonyl}-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-piperidine-4-carboxylic acid ethylesterYield 48%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of diethanolamine (2.1 g, 20 mmol), 4-(2-piperidin-1-yl-ethoxy)-benzyl chloride (5.9 g, 20 mmol) and KCO3 (10 g, excess) was refluxed in acetone (100 ml) for 24 hrs. At the end, reaction mixture was cooled to room temperature and filtered. It was concentrated to dryness and redissolved in touene (200 ml) and thionyl chloride (6.75 g, 50 mmol). It was heated to 80° C. for 1 hr and the separated brown solid, bis-(2-chloro-ethyl)-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-amine was filtered and dried. The crude product was taken to next step with out purification. Yield: 7.0 g, (89%). 4-{[4-(2-Butynyloxy)phenyl]sulfonyl}-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-piperidine-4-carboxylic acid ethylester was was prepared according to the general method as outlined in example 1 (step 6), starting from ethyl{[4-(2-butynyloxy)phenyl]sulfonyl}acetate (2.9 g, 10.0 mmol) and bis-(2-chloro-ethyl)-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-amine dihydrochloride (4.3 g, 10 mmol), 2.8 g of product (brown oil) was isolated. Yield 48%; MS: 583 (M+H)+

Workup

  1. customAt the end, reaction mixture
  2. filtrationfiltered
  3. concentrationIt was concentrated to dryness
  4. temperatureIt was heated to 80° C. for 1 hr
  5. filtrationthe separated brown solid, bis-(2-chloro-ethyl)-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-amine was filtered
  6. customdried
  7. customThe crude product was taken to next step with out purification

Sources & evidence

ORD record
ord-82cc929fc9a44c91accf6eb14b3c5759
Source dataset
uspto-grants-2002_03
Patent number
US06358980B1

Reaction notes

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