Sodium Hydroxide → Tert-butoxy[4-(2-hydroxy-4-methylphenyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid

HRID 2406401Notes

Reaction equation

HRID 2406401 reaction equation
[C:1]([O:5][CH:6]([C:12]1[C:13]([C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][C:27]=2[OH:33])=[C:14]2[C:21]3[CH2:22][CH2:23][CH2:24][CH2:25][C:20]=3[S:19][C:15]2=[N:16][C:17]=1[CH3:18])[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>C(O)C.O1CCCC1>[C:1]([O:5][CH:6]([C:12]1[C:13]([C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][C:27]=2[OH:33])=[C:14]2[C:21]3[CH2:22][CH2:23][CH2:24][CH2:25][C:20]=3[S:19][C:15]2=[N:16][C:17]=1[CH3:18])[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 136372356Ethyl tert-butoxy[4-(2-hydroxy-4-methylphenyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetate

Product 1

HCID 136372357Tert-butoxy[4-(2-hydroxy-4-methylphenyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acidYield 38%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of the major diastereoisomeric pair of ethyl tert-butoxy[4-(2-hydroxy-4-methylphenyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetate (Step 9, 214 mg, 458 μmol) in ethanol (5 mL) and tetrahydrofuran (5 mL) was added a solution of sodium hydroxide (2 N, aqueous, 2 mL, 2.75 mmol) and the reaction was stirred at 60° C. for 18 hours. The reaction was concentrated in vacuo until all organic solvents had been removed, the aqueous residue was then acidified with hydrochloric acid (2 N, aqueous) to pH 2. The precipitated solid was collected by filtration and washed with tert-butyl methyl ether (10 mL) and dried in vacuo to give a mixture of diastereoisomers of the title compound as a white solid, 76 mg, in a 38% yield. LC-MS (12 min acidic) 5.51 mins 81% pure by UV, ES+/APCI+ 440, ES−/APCI− 438. 1H NMR (400 MHz, CDCl3) δ ppm 1.04 (s, 9H) 1.66-1.88 (m, 4H) 2.09-2.21 (m, 2H) 2.40 (s, 3H) 2.73 (s, 3H) 2.82 (t, 2H) 5.33 (s, 1H) 6.78 (s, 1H) 6.85 (d, 1H) 7.36 (d, 1H).

Workup

  1. concentrationThe reaction was concentrated in vacuo until all organic solvents
  2. customhad been removed
  3. filtrationThe precipitated solid was collected by filtration
  4. washwashed with tert-butyl methyl ether (10 mL)
  5. customdried in vacuo
  6. customto give

Sources & evidence

ORD record
ord-19a5fe6788d940ed8544c13863966ace
Source dataset
uspto-grants-2014_08
Patent number
US08809363B2

Reaction notes

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