Sodium Hydroxide → HCID 67607642, compound

HRID 63966Notes

Reaction equation

HRID 63966 reaction equation
[OH-].[Na+].[C:3]([O:7][C@@H:8]([C:13]1[C:14]([C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=2)=[C:15]2[C:22]3[CH2:23][CH2:24][CH2:25][CH2:26][C:21]=3[S:20][C:16]2=[N:17][C:18]=1[CH3:19])[C:9]([O:11]C)=[O:10])([CH3:6])([CH3:5])[CH3:4]>>[C:3]([O:7][C@@H:8]([C:13]1[C:14]([C:27]2[CH:28]=[CH:29][C:30]([C:33]([F:35])([F:36])[F:34])=[CH:31][CH:32]=2)=[C:15]2[C:22]3[CH2:23][CH2:24][CH2:25][CH2:26][C:21]=3[S:20][C:16]2=[N:17][C:18]=1[CH3:19])[C:9]([OH:11])=[O:10])([CH3:6])([CH3:4])[CH3:5]

Participants

3

Reactant 2

HCID 14798Sodium HydroxideHCID 67607979(S)-methyl 2-(tert-butoxy)-2-(2-methyl-4-(4-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydro benzo[4,5]thieno[2,3-b]pyridin-3-yl)acetate

Product 1

HCID 67607642HCID 67607642, compoundYield 56.3%

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-(tert-butoxy)-2-(2-methyl-4-(4-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydro benzo[4,5]thieno[2,3-b]pyridin-3-yl)acetate (75 mg, 0.15 mmol) in 1:1 tetrahydrofuran/industrial methylated spirit (4 mL) at room temperature. The resulting mixture was heated at 60° C. 1.5 h. The resulting solution was concentrated in vacuo and the residue was dissolved in water (10 mL). The aqueous solution was adjusted to pH 4 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 flash column chromatography on silica eluting with methanol in dichloromethane (5%) to give the title compound (40.3 mg, 56%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ=1.01 (s, 9H), 1.89-1.30 (m, 6H), 2.71 (s, 3H), 2.90-2.75 (m, 2H), 5.02 (s, 1H), 7.48-7.34 (m, 1H), 7.90-7.64 (m, 3H). LCMS (run time=5 minutes, basic): Rt=3.30 minutes; m/z 478.01 [M+H+].

Workup

  1. custom1.5 h
  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 4 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 flash column chromatography on silica eluting with methanol in dichloromethane (5%)

Sources & evidence

ORD record
ord-31f7aa7e606a4731b5b83878b33c1ac8
Source dataset
uspto-grants-2016_09
Patent number
US09447116B2

Reaction notes

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