Sodium Hydroxide → (2S)-2-[4-(4-bromophenyl)-2-methyl-5,6,7,8-tetrahydrobenzothiopheno[2,3-b]pyridin-3-yl]-2-tert-butoxy-acetic acid

HRID 63968Notes

Reaction equation

HRID 63968 reaction equation
[OH-].[Na+].[Br:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:15]([C@H:16]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[C:17]([O:19]C)=[O:18])=[C:14]([CH3:26])[N:13]=[C:12]3[S:27][C:28]4[CH2:33][CH2:32][CH2:31][CH2:30][C:29]=4[C:11]=23)=[CH:6][CH:5]=1>>[Br:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[C:15]([C@H:16]([O:21][C:22]([CH3:24])([CH3:23])[CH3:25])[C:17]([OH:19])=[O:18])=[C:14]([CH3:26])[N:13]=[C:12]3[S:27][C:28]4[CH2:33][CH2:32][CH2:31][CH2:30][C:29]=4[C:11]=23)=[CH:8][CH:9]=1

Participants

3

Reactant 2

HCID 14798Sodium HydroxideHCID 69672886HCID 69672886, compound

Product 1

HCID 67606536(2S)-2-[4-(4-bromophenyl)-2-methyl-5,6,7,8-tetrahydrobenzothiopheno[2,3-b]pyridin-3-yl]-2-tert-butoxy-acetic acidYield 34.5%

Conditions

Temperature
60 °C

Procedure

1 M Aqueous sodium hydroxide solution (1.6 mL, 1.6 mmol) was added to a solution of (S)-methyl 2-(4-(4-bromophenyl)-2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-b]pyridin-3-yl)-2-(tert-butoxy)acetate (83 mg, 0.16 mmol) in 1:1 tetrahydrofuran/industrial methylated spirit (4 mL) at room temperature. The resulting mixture was heated to 60° C. and stirred at 60° C. 2 hours. The resulting solution was concentrated in vacuo and the residue was dissolved in water (10 mL). The aqueous solution was adjusted to pH 5 by the addition of 2 M aqueous hydrochloric acid solution and the resulting suspension was extracted with dichloromethane (20 mL). The organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo to give the crude product as a pale yellow solid. This was purified by trituration with industrial methylated spirit (5 mL). The resulting solid was collected by filtration to give the title compound (27 mg, 34%) as a white solid. 1H NMR (400 MHz, CDCl3) δ=1.02 (s, 9H), 2.00-1.40 (m, 6H), 2.69 (s, 3H), 2.83-2.70 (m, 2H), 5.11 (s, 1H), 7.25-7.06 (m, 1H), 7:63-7.42 (m, 3H). LCMS (run time=5 minutes, basic): Rt=3.19 minutes; m/z 490.00 [M+H+].

Workup

  1. custom2 hours
  2. concentrationThe resulting solution was concentrated in vacuo
  3. dissolutionthe residue was dissolved in water (10 mL)
  4. additionThe aqueous solution was adjusted to pH 5 by the addition of 2 M aqueous hydrochloric acid solution
  5. extractionthe resulting suspension was extracted with dichloromethane (20 mL)
  6. washThe organic layer was washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customto give the crude product as a pale yellow solid
  10. customThis was purified by trituration with industrial methylated spirit (5 mL)
  11. filtrationThe resulting solid was collected by filtration

Sources & evidence

ORD record
ord-ec7d798a936e4eaf86de26111f74f417
Source dataset
uspto-grants-2016_09
Patent number
US09447116B2

Reaction notes

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