Hydrochloric Acid → (2S)-tert-butoxy(4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)acetic acid

HRID 63940Notes

Reaction equation

HRID 63940 reaction equation
C([C@@H]1COC(=O)N1[C:14](=[O:36])[C@@H:15]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[C:16]1[C:17]([I:30])=[C:18]2[C:25]3[CH2:26][CH2:27][CH2:28][CH2:29][C:24]=3[S:23][C:19]2=[N:20][C:21]=1[CH3:22])C1C=CC=CC=1.O.[OH-].[Li+].OO.S([O-])([O-])=[O:43].[Na+].[Na+].Cl>O1CCCC1.O>[C:32]([O:31][C@@H:15]([C:16]1[C:17]([I:30])=[C:18]2[C:25]3[CH2:26][CH2:27][CH2:28][CH2:29][C:24]=3[S:23][C:19]2=[N:20][C:21]=1[CH3:22])[C:14]([OH:36])=[O:43])([CH3:35])([CH3:34])[CH3:33]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 24437Sodium SulfiteHCID 168937Lithium hydroxide, monohydrateHCID 69672766(4R)-4-benzyl-3-[(2S)-2-tert-butoxy-2-(4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)acetyl]-1,3-oxazolidin-2-one

Product 1

HCID 69672990(2S)-tert-butoxy(4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)acetic acidYield 65%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (4R)-4-benzyl-3-[(2S)-2-tert-butoxy-2-(4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)acetyl]-1,3-oxazolidin-2-one (Preparation 13B, 21.36 g, 34.53 mmol) in tetrahydrofuran (400 mL) and water (130 mL) at 0° C. was added dropwise a solution of lithium hydroxide hydrate (3.04 g, 72.52 mmol) and hydrogen peroxide (27% aqueous, 16.4 mL, 145.04 mmol). The resulting solution was stirred at 0° C. for 15 minutes, then for 2 hours at room temperature. A saturated solution of sodium sulphite (500 mL) was added followed by water (500 mL), and the mixture stirred for 15 minutes. The mixture was acidified to pH 4 by the addition of 6 M hydrochloric acid. The mixture was extracted with dichloromethane (4×500 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The resulting white solid was crystallised from methylated spirits (150 mL) with heating at reflux for 5 minutes. The mixture was allowed to cool to room temperature overnight. The resulting solid was collected by filtration and washed with cold methylated spirits and dried in vacuo to give the title compound as a white solid, 10.25 g, in a 65% yield.

Workup

  1. waitfor 2 hours at room temperature
  2. stirringthe mixture stirred for 15 minutes
  3. extractionThe mixture was extracted with dichloromethane (4×500 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe resulting white solid was crystallised from methylated spirits (150 mL)
  7. temperaturewith heating
  8. temperatureat reflux for 5 minutes
  9. temperatureto cool to room temperature overnight
  10. filtrationThe resulting solid was collected by filtration
  11. washwashed with cold methylated spirits
  12. customdried in vacuo

Sources & evidence

ORD record
ord-81e6ac4bb4ac48ab8d5f87db3c9f63b5
Source dataset
uspto-grants-2016_09
Patent number
US09447116B2

Reaction notes

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