Hydrochloric Acid → HCID 66749017, compound

HRID 2402149Notes

Reaction equation

HRID 2402149 reaction equation
[C:1]([C:3]1[C:4]([CH:19]([C:21]2[CH:30]=[CH:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=2)[CH3:20])=[C:5]([C:14]([O:16]CC)=[O:15])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2].[OH-].[Na+].Cl>O1CCCC1.CO.O>[C:1]([C:3]1[C:4]([CH:19]([C:21]2[CH:30]=[CH:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=2)[CH3:20])=[C:5]([C:14]([OH:16])=[O:15])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66748117HCID 66748117, compound

Product 1

HCID 66749017HCID 66749017, compoundYield 97.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 4-cyano-5-(morpholin-4-yl)-3-[1-(2-naphthyl)ethyl]thiophene-2-carboxylate (13.3 g, 31.6 mmol) in tetrahydrofuran (200 mL) and methanol (150 mL) was stirred until the mixture turned into a clear solution. To the solution was added 1.000 M sodium hydroxide in water (158 mL). The resulting turbid mixture was vigorously stirred at rt for 12 h. The volatiles were removed under reduced pressure, and the resulting aqueous solution was acidified by addition of 12.0 M of hydrochloric acid in water (15.9 mL, 191 mmol) at 0° C., and then extracted with EtOAc (×3). The combined organic layers were washed with 1M HCl soln, dried, and concentrated to provide 4-cyano-5-(morpholin-4-yl)-3-[1-(2-naphthyl)ethyl]thiophene-2-carboxylic acid as a white solid (12.1 g, 97.5% yield). 250 mg of the racemic mixture was purified on chiral prep HPLC to provide each enantiomer (115 mg each, >95% ee) (OJ column, elution with 85/5/10/0.1% hexane/iPrOH/EtOH/Et2NH). LCMS: (AA) ES+ 393; 1H NMR (400 MHz, MeOD) δ 7.85-7.76 (m, 3H), 7.76-7.71 (d, J=8.6 Hz, 1H), 7.49-7.38 (m, 2H), 7.38-7.29 (dd, J=8.5, 1.7 Hz, 1H), 5.90-5.74 (q, J=7.3 Hz, 1H), 3.82-3.69 (m, 4H), 3.52-3.43 (dd, J=5.8, 4.0 Hz, 4H), 1.91-1.80 (d, J=7.3 Hz, 3H).

Workup

  1. customThe volatiles were removed under reduced pressure
  2. extractionextracted with EtOAc (×3)
  3. washThe combined organic layers were washed with 1M HCl soln
  4. customdried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-fa494ad8fa5444ee94f644e1837eb7c0
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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