Triethylamine → HCID 57565317, compound

HRID 605518Notes

Reaction equation

HRID 605518 reaction equation
ClS(O)(=O)=O.[CH3:6][O:7][C:8](=[O:23])[CH2:9][CH:10]1[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[C:15]([S:19](Cl)(=[O:21])=[O:20])[CH:16]=2)[CH2:11]1.[CH3:24][O:25][C:26](=[O:41])[CH2:27][CH:28]1[CH2:36][C:35]2[C:30](=[CH:31][CH:32]=[CH:33][C:34]=2[S:37](Cl)(=[O:39])=[O:38])[CH2:29]1.[F:42][C:43]([F:57])([F:56])[C:44]1[CH:49]=[CH:48][C:47]([N:50]2[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]2)=[CH:46][CH:45]=1.C(N(CC)CC)C>C1COCC1.CN(C1C=CN=CC=1)C>[CH3:6][O:7][C:8](=[O:23])[CH2:9][CH:10]1[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[C:15]([S:19]([N:53]3[CH2:52][CH2:51][N:50]([C:47]4[CH:46]=[CH:45][C:44]([C:43]([F:56])([F:57])[F:42])=[CH:49][CH:48]=4)[CH2:55][CH2:54]3)(=[O:21])=[O:20])[CH:16]=2)[CH2:11]1.[CH3:24][O:25][C:26](=[O:41])[CH2:27][CH:28]1[CH2:36][C:35]2[C:30](=[CH:31][CH:32]=[CH:33][C:34]=2[S:37]([N:53]2[CH2:52][CH2:51][N:50]([C:47]3[CH:46]=[CH:45][C:44]([C:43]([F:56])([F:57])[F:42])=[CH:49][CH:48]=3)[CH2:55][CH2:54]2)(=[O:39])=[O:38])[CH2:29]1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 24638Chlorosulfonic acidHCID 1217181-(4-(Trifluoromethyl)phenyl)piperazineHCID 85864988HCID 85864988, compoundHCID 86245824HCID 86245824, compound

Product 2

HCID 57565317HCID 57565317, compoundYield 19%HCID 67046329HCID 67046329, compoundYield 6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Indanyl-2-acetic acid methyl ester (1.0 g, 5.26 mmol) was added to a stirring solution of chlorosulfonic acid (5 mL) at 0° C. The solution was stirred at 0° C. for 0.5 h, then room temperature for 3 h. The resulting solution was poured slowly over ice and extracted with diethyl ether (3×100 mL). The combined organic layers were dried (Na2SO4) and concentrated to afford a mixture of 5-chlorosulfonyl-indan-2-acetic acid methyl ester and 4-chlorosulfonyl-indan-2-acetic acid methyl ester (1.38 g, 4.78 mmol, 91%). The sulfonyl chloride mixture was taken on to the next step without further purification. The mixture of sulfonyl chlorides (370 mg, 1.28 mmol) were dissolved in dry THF (10 mL). To this solution was added 1-(4-trifluoromethylphenyl)piperazine (315 mg, 1.37 mmol), triethylamine (600 μL, 4.3 mmol) and DMAP (catalytic amount). The reaction was stirred at room temperature for 1 h, concentrated and directly purified by silica gel flash column chromatography to separate the regioisomers (25% ethyl acetate in hexanes) affording {5-[4-(4-trifluoromethyl-phenyl)-piperazine-1-sulfonyl]-indan-2-yl}-acetic acid methyl ester (118 mg, 19%) and {4-[4-(4-trifluoromethyl-phenyl)-piperazine-1-sulfonyl]-indan-2-yl}-acetic acid methyl ester (40 mg, 6%) as clear colorless oils. {5-[4-(4-trifluoromethyl-phenyl)-piperazine-1-sulfonyl]-indan-2-yl}-acetic acid methyl ester: 1H NMR (400 MHz, CDCl3) 7.57 (s, 1H), 7.56 (d, 1H), 7.45 (d, 2H), 7.33 (d, 1H), 6.87 (d, 2H), 3.69 (s, 3H), 3.33 (m, 4H), 3.21 (dd, 2H), 3.14 (m, 4H), 2.95 (m, 1H), 2.71 (dd, 2H), 2.52 (d, 2H).

Workup

  1. waitroom temperature for 3 h
  2. additionThe resulting solution was poured slowly over ice
  3. extractionextracted with diethyl ether (3×100 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. concentrationconcentrated
  6. customto afford
  7. customThe sulfonyl chloride mixture was taken on to the next step without further purification
  8. stirringThe reaction was stirred at room temperature for 1 h
  9. concentrationconcentrated
  10. customdirectly purified by silica gel flash column chromatography
  11. customto separate the regioisomers (25% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-111adc34c44242debd1ea511873cf53a
Source dataset
uspto-grants-2011_03
Patent number
US07915253B2

Reaction notes

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