Triethylamine → 3-(4-Fluorobenzenesulfonyl)-2,8-dimethyl-1-thia-3,8-diazaspiro[4.5]-decane

HRID 1187320Notes

Reaction equation

HRID 1187320 reaction equation
[CH3:1][CH:2]1[NH:6][CH2:5][C:4]2([CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]2)[S:3]1.C(N(CC)CC)C.[F:20][C:21]1[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1>ClCCl>[F:20][C:21]1[CH:26]=[CH:25][C:24]([S:27]([N:6]2[CH2:5][C:4]3([CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]3)[S:3][CH:2]2[CH3:1])(=[O:29])=[O:28])=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 95884-Fluorobenzenesulfonyl chlorideHCID 669939622,8-Dimethyl-1-thia-3,8-diazaspiro[4.5]decane

Product 1

HCID 468468003-(4-Fluorobenzenesulfonyl)-2,8-dimethyl-1-thia-3,8-diazaspiro[4.5]-decane

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

2,8-dimethyl-1-thia-3,8-diaza-spiro[4.5]decane (573 mg, 3.08 mmol) was dissolved in dry dichloromethane (2 ml) under an argon atmosphere. Distilled triethylamine (644 μl, 4.62 mmol) was added and the resulting solution was cooled to 0° C. A solution of p-fluorobenzenesulfonyl chloride (600 mg, 3.08 mmol) in dry dichloromethane (2 ml) was added dropwise with a syringe. The reaction flask was allowed to warm to room temperature with stirring, and a white solid started to precipitate. After 1 h of stirring, dichloromethane (50 ml) was added and the resulted solution was washed with water (2×10 ml). The organic phase was dried with anhydrous magnesium sulfate, filtered and evaporated to give the crude mixture as an oil. The crude product was purified by flash chromatography (silica, CH2Cl2/MeOH/NH4OH 93/7/1) to provide AF716 (496 mg, 98.8% chemical purity) as an off-white powder. 1H NMR (CDCl3, 300 MHz) δ 7.89-7.85 (m, 2H, two CHCSO2), 7.27-7.19 (m, 2H, CHCF), 5.02 (q, J=6.12 Hz, 1H, CH—CH3), 3.66 (d, J=11.37 Hz, 1H, CHHNS), 3.48 (d, J=11.37 Hz, 1H, CHHNS), 2.72-2.50 (m, 2H, CH2NCH3), 2.25 (s, 3H, NCH3), 2.16-2.07 (m, 2H, CH2NCH3), 1.95-1.88 (m, 2H, CH2CS), 1.55 (d, J=6.12 Hz, 3H, CH3CH), 1.48 (m, 2H, CH2CS) ppm; 13C NMR (CDCl3, 300 MHz) δ 166.92 and 163.54 (C), 130.05 (CH), 129.93 (CH), 129.58 (C), 116.60 (CH), 116.30 (CH), 60.76 (C), 60.24 (CH), 54.05 (CH2), 53.22 (CH2), 46.03 (CH3), 37.16 (CH2), 37.05 (CH2), 25.56 (CH3) ppm.

Workup

  1. temperatureto warm to room temperature
  2. customto precipitate
  3. stirringAfter 1 h of stirring
  4. additiondichloromethane (50 ml) was added
  5. washthe resulted solution was washed with water (2×10 ml)
  6. dry with materialThe organic phase was dried with anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-9aa955f1eeff46299eb60451b85bd41d
Source dataset
uspto-grants-2014_03
Patent number
US08673931B2

Reaction notes

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