Ethylene Glycol → HCID 86591408, compound

HRID 1677820Notes

Reaction equation

HRID 1677820 reaction equation
[O:1]=[C:2]1[CH2:6][CH2:5][N:4]([S:7]([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH2:3]1.[CH2:18](O)[CH2:19][OH:20]>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[O:20]1[C:2]2([CH2:6][CH2:5][N:4]([S:7]([C:10]3[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=3)(=[O:9])=[O:8])[CH2:3]2)[O:1][CH2:18][CH2:19]1

Participants

5

Reactant 2

HCID 174Ethylene GlycolHCID 67354698HCID 67354698, compound

Product 1

HCID 86591408HCID 86591408, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 1140TolueneSolvent

Procedure

4-[(3-oxo-1-pyrrolidinyl)sulfonyl]benzonitrile 23b (11.6 g, 46.3 mmol) was suspended in toluene (110 ml) and stirred at room temp. Ethylene glycol (6.2 ml, 6.9 g, 111 mmol) and para-toluene sulphonic acid monohydrate (100 mg, 0.53 mmol) were added. The reaction mixture was heated to reflux under Dean-Stark conditions and monitored by water collection and TLC (5% methanol in DCM). If necessary for the completion of the reaction (typically within 3 h), further portions of p-TSA were added. When complete the reaction mixture was washed with saturated sodium bicarbonate solution (55 ml) and water (2×55 ml). The organic layer was filtered through cotton wool and then concentrated in vacuo to approximately 50 ml or until precipitation started. Hexane (150 ml) was added and the suspension stirred at 0-5° C. for 10-20 min, filtered and washed with hexane (2×50 ml). The residue was air dried to yield 13.0 g (96%) ketal 4-(1,4-dioxa-7-azaspiro[4.4]non-7-ylsulfonyl)benzonitrile 23c. 4-(1,4-dioxa-7-azaspiro[4.4]non-7-ylsulfonyl)benzonitrile 23c was progressed according to the procedure described for example 7b which finally leads to 4-chloro-N-(4-{[3-({2-[3-(trifluoromethyl)phenyl]ethyl}amino)-1-pyrrolidinyl]sulfonyl}benzyl)benzamide 23. M/Z APCI 566.0 (M+1), 564.2 (M−1), 1H-NMR (DMSO-d6) δ9.57 (m, 2H, H—N15), 9.42 (t, 1H, H—N5, 3J=5.92 Hz), 7.99 (d, 2H, 3J=8.65 Hz, H—C2, 3), 7.82 (d, 2H, H—C8, 9), 7.71-7.59 (m, 8H, H—C1,4,7,10,18,19,20,21), 4.62 (d, 2H, 3J=5.92 Hz, H—C6), 3.75 (m, 1H, H—C12), 3.53-3.33 (m, 2H under DMSO-H2O signal, H—C16), 3.27-3.03 (m, 6H, H—C11, 14, 17), 2.17 (m, 1H, Ha—C13), 2.04 (m, 1H, Hb—C13).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux under Dean-Stark conditions
  3. custommonitored by water collection and TLC (5% methanol in DCM)
  4. customIf necessary for the completion of the reaction (typically within 3 h), further portions of p-TSA
  5. additionwere added
  6. washWhen complete the reaction mixture was washed with saturated sodium bicarbonate solution (55 ml) and water (2×55 ml)
  7. filtrationThe organic layer was filtered through cotton wool
  8. concentrationconcentrated in vacuo to approximately 50 ml or until precipitation
  9. additionHexane (150 ml) was added
  10. stirringthe suspension stirred at 0-5° C. for 10-20 min
  11. filtrationfiltered
  12. washwashed with hexane (2×50 ml)
  13. customdried

Sources & evidence

ORD record
ord-ce6c4cd03d4e4690ad85963936ebfb77
Source dataset
uspto-grants-2011_08
Patent number
US08008341B2

Reaction notes

Loading…