4-Toluenesulfonyl chloride → Toluene-4-sulfonic acid 3-(4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutylmethyl ester

HRID 1241507Notes

Reaction equation

HRID 1241507 reaction equation
[N:1]1([CH2:6][C:7]2[CH:12]=[CH:11][C:10]([CH:13]3[CH2:16][CH:15]([CH2:17][OH:18])[CH2:14]3)=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[C:26]1([CH3:36])[CH:31]=[CH:30][C:29]([S:32](Cl)(=[O:34])=[O:33])=[CH:28][CH:27]=1>ClCCl.CN(C)C1C=CN=CC=1>[N:1]1([CH2:6][C:7]2[CH:12]=[CH:11][C:10]([CH:13]3[CH2:14][CH:15]([CH2:17][O:18][S:32]([C:29]4[CH:30]=[CH:31][C:26]([CH3:36])=[CH:27][CH:28]=4)(=[O:34])=[O:33])[CH2:16]3)=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 21934866[3-(4-Pyrrolidin-1-ylmethyl-phenyl)-cyclobutyl]-methanol

Product 1

HCID 11429478Toluene-4-sulfonic acid 3-(4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutylmethyl esterYield 93%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of [3-(4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutyl]-methanol (0.56 g, 2.3 mmol) prepared above in 5 mL of dichlormethane was added triethyl amine (1.6 mL, 2.7 mmol) followed by 4-(dimethyl amino)pyridine (2.8 mg, 0.23 mmol) and p-toluene sulfonyl chloride (0.52 g, 2.7 mmol). After 1 hr the reaction was quenched with a saturated aqueous solution of NaHCO3. The reaction was diluted and extracted with dichloromethane. The organic layers were dried over magnesium sulfate, filtered through a fritted funnel, and concentrated under reduced pressure. Purification of this material was accomplished by flash column chromatography, using a 40 g ISCO column, eluting with a gradient of 4%, 6%, and 10% MeOH/CH2Cl2. The product containing fractions were collected and concentrate under reduced pressure to give the title compound (0.82 g, 93% yield) as a colorless oil and a mixture of cis:trans isomers.

Workup

  1. customAfter 1 hr the reaction was quenched with a saturated aqueous solution of NaHCO3
  2. additionThe reaction was diluted
  3. extractionextracted with dichloromethane
  4. dry with materialThe organic layers were dried over magnesium sulfate
  5. filtrationfiltered through a fritted funnel
  6. concentrationconcentrated under reduced pressure
  7. customPurification of this material
  8. washeluting with a gradient of 4%, 6%, and 10% MeOH/CH2Cl2
  9. additionThe product containing fractions
  10. customwere collected
  11. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-c5c43fef38c94e6f8338387ff113f11c
Source dataset
uspto-grants-2006_10
Patent number
US07115600B2

Reaction notes

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