Acetic Acid → HCID 131727467, compound

HRID 1983908Notes

Reaction equation

HRID 1983908 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH:10]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[CH2:13][NH:12][CH2:11]3)[CH:8]=[CH:9][C:2]1=2.C([O:22][C:23]1([O:26][Si](C)(C)C)[CH2:25][CH2:24]1)C.[C:31]([OH:34])(=[O:33])C.C([BH3-])#N.[Na+]>O>[C:23]([OH:22])(=[O:26])/[CH:25]=[CH:24]/[C:31]([OH:34])=[O:33].[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH:10]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[CH2:13][N:12]([CH:23]4[CH2:25][CH2:24]4)[CH2:11]3)[CH:8]=[CH:9][C:2]1=2

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 11536296HCID 11536296, compound

Product 1

HCID 131727467HCID 131727467, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 4-benzo[b]thiophen-5-yl-1,2,3,4-tetrahydroisoquinoline (250 mg, 0.94 mmol, the preparation of which was described in Example 20), (1-ethoxycyclopropoxy)trimethylsilane (987 mg, 5.66 mmol), acetic acid (600 mg, 9.42 mmol), sodium cyanoborohydride (296 mg, 4.72 mmol), and molecular sieves (4 Å) was heated at reflux temperature for 16 hours, then cooled to room temperature. The mixture was treated with water, concentrated in vacuo, the residue dissolved in ethyl acetate and washed with 1N NaOH solution, then brine. The organic layer was dried over magnesium sulfate, concentrated and the residue purified by column chromatography (SiO2, 12 g, 85% to 0% hexanes/ethyl acetate) to provide the desired tetrahydroisoquinoline (87 mg, 30%). This material was dissolved in methanol and treated with a solution of fumaric acid in methanol (5 mL) at 0° C. The solution was stirred at room temperature for 12 hours, then concentrated, and the solid was washed with diethyl ether providing 4-benzo[b]thiophen-5-yl-2-cyclopropyl-1,2,3,4-tetrahydroisoquinoline, fumarate salt (100 mg, 95.5% AUC HPLC): 1H NMR (CD3OD, 300 MHz) δ 7.84 (d, J=8.3 Hz, 1H), 7.70 (d, J=1.4 Hz, 1H), 7.56 (d, J=5.5 Hz, 1H), 7.32 (d, J=5.1 Hz, 1H), 7.20-7.07 (m, 4H), 6.84 (d, J=7.5 Hz, 1H), 6.73 (s, 2H), 4.48-4.43 (m, 1H), 4.23-4.10 (m, 2H), 3.57-3.47 (m, 2H), 3.13-3.06 (m, 1H), 2.21-2.18 (m, 1H), 0.71-0.64 (m, 4H); ESI-MS m/z=306 [+H]+.

Workup

  1. customthe preparation of which
  2. temperaturewas heated
  3. temperatureat reflux temperature for 16 hours
  4. concentrationconcentrated in vacuo
  5. dissolutionthe residue dissolved in ethyl acetate
  6. washwashed with 1N NaOH solution
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. concentrationconcentrated
  9. customthe residue purified by column chromatography (SiO2, 12 g, 85% to 0% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-daed3688782e425ab6b522678fac9197
Source dataset
uspto-grants-2009_06
Patent number
US07541357B2

Reaction notes

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