Ammonium Chloride → (-)-4-Benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-ol

HRID 402122Notes

Reaction equation

HRID 402122 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][C:16]([O:20]C)=[CH:17][CH:18]=4)[CH2:13][N:12]([CH3:22])[CH2:11]3)[CH:8]=[CH:9][C:2]1=2.C([S-])C.[Na+].[NH4+].[Cl-]>CN(C=O)C>[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH:10]3[C:19]4[C:14](=[CH:15][C:16]([OH:20])=[CH:17][CH:18]=4)[CH2:13][N:12]([CH3:22])[CH2:11]3)[CH:8]=[CH:9][C:2]1=2

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 4459711Sodium ethanethiolateHCID 689943124-Benzo[b]thiophen-5-yl-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 68997664(-)-4-Benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-olYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of (−)-4-benzo[b]thiophen-5-yl-7-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline (10.00 g, 32.3 mmol) which was obtained according to Step F in the preparation of Example 98 and sodium ethanethiolate (11.3 g, 134.3 mmol) in DMF (250 mL) was heated at 140° C. under an N2 atmosphere for 14 hours. The reaction mixture was cooled in an ice bath before addition of saturated NH4Cl (250 mL). The aqueous phase was extracted with DCM (3×750 mL) and the combined organic extracts washed with water (3×500 mL), brine, dried over Na2SO4 and concentrated in vacuo. The crude material was purified by silica gel column chromatography (eluent: 5% MeOH/CH2Cl2) to afford (−)-4-benzo[b]thiophen-5-yl-2-methyl-1,2,3,4-tetrahydroisoquinoline-7-ol (6.64 g, 70%) as an orange-brown solid: 1H NMR (300 MHz, CDCl3) δ 7.76 (d, J=8.3 Hz, 1H), 7.62 (s, 1H), 7.40 (d, J=5.4 Hz, 1H), 7.26-7.20 (m, 2H), 7.13 (d, J=8.4 Hz, 1H), 6.66 (d, J=8.3 Hz, 1H), 6.50-6.40 (m, 2H), 4.34 (dd, J=9.0, 6.0 Hz, 1H), 3.68 (d, J=15.0 Hz, 1H), 3.54 (d, J=15.0 Hz, 1H), 3.11 (dd, J=11.5, 5.7 Hz, 1H), 2.58 (dd, J=11.3, 9.7 Hz, 1H), 2.43 (s, 3H); ESI-MS m/z=296 [M+H]+.

Workup

  1. customwas obtained
  2. extractionThe aqueous phase was extracted with DCM (3×750 mL)
  3. washthe combined organic extracts washed with water (3×500 mL), brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by silica gel column chromatography (eluent: 5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-77d681627fc64c3781886c326e47e3fd
Source dataset
uspto-grants-2014_06
Patent number
US08741901B2

Reaction notes

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