Sodium Hydroxide → HCID 66972325, compound

HRID 1985797Notes

Reaction equation

HRID 1985797 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][S:8][CH2:9][C@H:10]([NH:15][CH:16]([C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)[C:17]([F:20])([F:19])[F:18])[C:11]([O:13]C)=[O:12].[OH-].[Na+]>CO>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][S:8][CH2:9][C@H:10]([NH:15][CH:16]([C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)[C:17]([F:20])([F:18])[F:19])[C:11]([OH:13])=[O:12]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 66972577HCID 66972577, compound

Product 1

HCID 66972325HCID 66972325, compoundYield 66.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of methyl 3-(pyridin-2-ylmethylsulfanyl)-2(R)-[2,2,2-trifluoro-1(RS)-(4-fluorophenyl)ethylamino]propionate (0.64 g, 1.59 mmol) in methanol (9 mL) was added 1N sodium hydroxide (4.77 mL). The resulting solution was stirred for 2 h at ambient temperature and then methanol was removed in vacuo. The residue was portioned between water and ethyl acetate. The aqueous layer was extracted twice more with ethyl acetate and the combined organic layers were dried over magnesium sulfate. Removal of the solvents provided 3-(pyridin-2-ylmethylsulfanyl)-2(R)-[2,2,2-trifluoro-1(RS)-(4-fluorophenyl)ethylamino]propionic acid (0.410 g, 1.06 mmol) as a white solid which was a mixture of diastereomers. 3-(Pyridin-2-ylmethylsulfanyl)-2(R)-[2,2,2-trifluoro-1(RS)-(4-fluorophenyl)ethylamino]propionic acid was converted to of N-(1-cyano-cyclopropyl)-3-(pyridin-2-ylmethylsulfanyl)-2(R)-[2,2,2-trifluoro-1(RS)-(4-fluorophenyl)-ethylamino]propionamide by proceeding as described in Example 2, Step 8 above. N-(1-Cyanocyclopropyl)-3-pyridin-2-ylmethanesulfanyl-2(R)-(2,2,2-trifluoro-1(S)-4-fluorophenyl-ethylamino)propionamide (95 mg) was obtained from the diasteriomeric mixture by flash chromatography and was converted to the title compound (50 mg) by proceeding as described in Example 1, Step 6 above.

Workup

  1. custommethanol was removed in vacuo
  2. extractionThe aqueous layer was extracted twice more with ethyl acetate
  3. dry with materialthe combined organic layers were dried over magnesium sulfate
  4. customRemoval of the solvents

Sources & evidence

ORD record
ord-214934cfc5b34f1cbf464f922c8df351
Source dataset
uspto-grants-2009_06
Patent number
US07547701B2

Reaction notes

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