Hydrochloric Acid → HCID 19919627, compound

HRID 1648368Notes

Reaction equation

HRID 1648368 reaction equation
[C:1]1([CH2:7][CH2:8][N:9]2[CH2:14][CH2:13][N:12]([C:15]3[C:23]4[CH:22]=[C:21]([CH2:24]O)[S:20][C:19]=4[CH:18]=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:45]1(=[O:55])[NH:49][C:48](=[O:50])[C:47]2=[CH:51][CH:52]=[CH:53][CH:54]=[C:46]12.N(C(OCC)=O)=NC(OCC)=O.[ClH:68]>ClCCl.C(O)C.C(O)(=O)C.O1CCCC1>[ClH:68].[CH2:8]([N:9]1[CH2:10][CH2:11][N:12]([C:15]2[C:23]3[CH:22]=[C:21]([CH2:24][N:49]4[C:45](=[O:55])[C:46]5[C:47](=[CH:51][CH:52]=[CH:53][CH:54]=5)[C:48]4=[O:50])[S:20][C:19]=3[CH:18]=[CH:17][CH:16]=2)[CH2:13][CH2:14]1)[CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 15289957HCID 15289957, compound

Product 1

HCID 19919627HCID 19919627, compound

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Anhydrous tetrahydrofuran (30 mL) was added to a flask containing 4- [4- (2-phenylethyl ) -1-piperazinyl]benzo[b]thiophene-2-methanol (3.20 g, 9.08 mmol), triphenylphosphine (2.50 g, 9.53 mmol) and phthalimide (1.40 g, 9.53 mmol). The reaction was cooled to 0° C. in an ice bath and diethyl azodicarboxylate (1.5 mL, 9.53 mmol) was added over 3 min. The bath was removed after stirring under nitrogen for 20 min and allowed to stir at room temperature for 15.5 h. The reaction was concentrated in vacuo and the crude product was chromatographed using 40:60 ethyl acetate:hexane. The component with Rf of ca. 0.4 was isolated. The compound was rechromatographed to remove a by product using 95:5 dichloromethane:acetone, then using 5:95 acetic acid: ethyl acetate. the component with Rf of ca. 0.3 was isolated (3.26 g), along with acetic acid. The compound was dissolved in dichloromethane (75 mL), washed with saturated aqueous sodium bicarbonate (50 mL), dried over magnesium sulfate/sodium sulfate, filtered and concentrated in vacuo (2.80 g). A solution of product (1.00 g, 2.08 mmol) in a mixture of ethanol (50 mL) and dichloromethane (50 mL) was treated with 1.0M aqueous hydrochloric acid (2.10 mL) and concentrated in vacuo. The resulting solid was recrystallized from a mixture of methanol (50 mL), dichloromethane (80 mL) and water (8 drops) to yield the title compound (0.87 g). 1H NMR (DMSO-d6 +CD3OD+D2O): 7.85 (4H, m), 7.54 (1H, d, J=7.8 Hz), 7.45 (1H, s), 7.31 (6H, m), 6.96 (1H, d, J=7.8 Hz), 5.04 (2H, s), 3.60-3.10 (10H), 3.01 (2H, m) ppm. 13C NMR (DMSO-d6 +CD3OD+D2O): 168.56, 147.08, 141.37, 139,90, 135.89, 133.75, 131.94, 129.64, 127.93, 126.53, 124.35, 122.11, 118.74, 114.07, 57.78, 52.51, 49.74, 37.49, 30.53 ppm. IR (KBr): 2456, 2434, 1769, 1719, 1427, 1393, 1356 cm-1. CIMS (methane): 482 (100%).

Workup

  1. customThe bath was removed
  2. stirringto stir at room temperature for 15.5 h
  3. concentrationThe reaction was concentrated in vacuo
  4. customthe crude product was chromatographed
  5. customThe component with Rf of ca. 0.4 was isolated
  6. customThe compound was rechromatographed
  7. customto remove a by product
  8. customthe component with Rf of ca. 0.3 was isolated (3.26 g)
  9. washwashed with saturated aqueous sodium bicarbonate (50 mL)
  10. dry with materialdried over magnesium sulfate/sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo (2.80 g)
  13. concentrationconcentrated in vacuo
  14. customThe resulting solid was recrystallized from a mixture of methanol (50 mL), dichloromethane (80 mL) and water (8 drops)

Sources & evidence

ORD record
ord-3be47710112c4bbc9c08ee9b653fa004
Source dataset
uspto-grants-1995_07
Patent number
US05436246

Reaction notes

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