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

HRID 2406403Notes

Reaction equation

HRID 2406403 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]([CH:33]([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:32]=[CH:31][C:30]([CH:33]([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]([OH:11])=[O:10])([CH3:6])([CH3:4])[CH3:5]

Participants

3

Reactant 2

HCID 14798Sodium HydroxideHCID 67607847(S)-methyl 2-(tert-butoxy)-2-(4-(4-(difluoromethyl)phenyl)-2-methyl-5,6,7,8-tetrahydro benzo[4,5]thieno[2,3-b]pyridin-3-yl)acetate

Product 1

HCID 67609250(2S)-2-tert-butoxy-2-[4-[4-(difluoromethyl)phenyl]-2-methyl-5,6,7,8-tetrahydrobenzothiopheno[2,3-b]pyridin-3-yl]acetic acidYield 63%

Procedure

2 M Aqueous sodium hydroxide solution (1.93 mL, 3.86 mmol) was added to a solution of (S)-methyl 2-(tert-butoxy)-2-(4-(4-(difluoromethyl)phenyl)-2-methyl-5,6,7,8-tetrahydro benzo[4,5]thieno[2,3-b]pyridin-3-yl)acetate (183 mg, 0.39 mmol) in 1:1 tetrohydrofuran/industrial methylated spirit (4 mL) at room temperature. The resulting mixture stirred at room temperature for 64 h. The reaction mixture was partitioned between ethyl acetate (20 mL) and water (10 mL). The aqueous solution was adjusted to pH 4 by the addition of 2 M aqueous hydrochloric acid solution. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo to give the crude product as a pale orange solid. This was purified by flash column chromatography on silica eluting with methanol in dichloromethane (3-5%) to give the title compound (111 mg, 63%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ=1.01 (s, 9H), 1.90-1.35 (m, 6H), 2.70 (s, 3H), 2.85-2.78 (m, 2H), 5.07 (brs, 1H), 6.75 (t, 1H), 7.34-7.41 (brm, 1H), 7.61 (d, 2H), 7.80-7.70 (brm, 1H). LCMS (run time=5 minutes, basic): Rt=3.04 minutes; m/z 460.22 [M+H+].

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate (20 mL) and water (10 mL)
  2. additionThe aqueous solution was adjusted to pH 4 by the addition of 2 M aqueous hydrochloric acid solution
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (2×10 mL)
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customto give the crude product as a pale orange solid
  8. customThis was purified by flash column chromatography on silica eluting with methanol in dichloromethane (3-5%)

Sources & evidence

ORD record
ord-75f292a6ebc94c75a7a6a3fcbb1ae22b
Source dataset
uspto-grants-2014_08
Patent number
US08809363B2

Reaction notes

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