Lithium Hydroxide → HCID 44818729, compound

HRID 1951642Notes

Reaction equation

HRID 1951642 reaction equation
[CH3:1][C:2]1[S:9][C:8]2[CH:7]=[CH:6][N:5]([CH2:10][C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=3)[C:4]=2[C:3]=1[C:21](O)=[O:22].C[O:25][C:26](=[O:36])[C:27]1[CH:32]=[CH:31][C:30]([C@@H:33]([NH2:35])[CH3:34])=[CH:29][CH:28]=1.Cl.C(N=C=NCCCN(C)C)C.CN1CCOCC1.[Li+].[OH-]>CN(C=O)C.C1COCC1.O.CO>[CH3:1][C:2]1[S:9][C:8]2[CH:7]=[CH:6][N:5]([CH2:10][C:11]3[CH:12]=[CH:13][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:15][CH:16]=3)[C:4]=2[C:3]=1[C:21]([NH:35][C@H:33]([C:30]1[CH:31]=[CH:32][C:27]([C:26]([OH:25])=[O:36])=[CH:28][CH:29]=1)[CH3:34])=[O:22]

Participants

10

Reactant 5

HCID 3939Lithium HydroxideHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 17751895Methyl 4-((1S)-1-aminoethyl)benzoateHCID 671826242-Methyl-4-(4-(trifluoromethyl)benzyl)-4H-thieno[3,2-b]pyrrole-3-carboxylic acid

Product 1

HCID 44818729HCID 44818729, compoundYield 47%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 0.043 g of 2-methyl-4-(4-trifluoromethyl-benzyl)-4H-thieno[3,2-b]pyrrole-3-carboxylic acid, 0.060 g of (S)-4-(1-amino-ethyl)-benzoic acid methyl ester, 0.040 g of HOBT-hydrate, 0.054 g of ethyl-dimethylaminopropyl-carbodiimide hydrochloride (EDCI) and 0.060 ml of N-methylmorpholine in 2 ml of DMF was stirred at room temperature for 18 h. The reaction was then quenched with 1 ml of water and 2 ml of saturated NaHCO3 solution. The resulting mixture extracted with 15 ml of EtOAc. The organic layer was dried over Na2SO4, filtered, and concentrated to give the crude methyl ester which was dissolved in 2 ml THF, 2 mL MeOH and 0.5 mL water and treated with 0.5 mL of 1M LiOH solution. After stirring for 24 h at room temperature, the reaction mixture was concentrated under reduced pressure to remove THF and MeOH. The residue was diluted with 2 mL of water and treated with 0.3 mL of AcOH with vigorous stirring. After stirring for 2 h, the solid was collected by filtration and air-dried to give 0.029 g of the title compound as a white powder.

Workup

  1. customThe reaction was then quenched with 1 ml of water and 2 ml of saturated NaHCO3 solution
  2. extractionThe resulting mixture extracted with 15 ml of EtOAc
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude methyl ester which
  7. stirringAfter stirring for 24 h at room temperature
  8. concentrationthe reaction mixture was concentrated under reduced pressure
  9. customto remove THF and MeOH
  10. additionThe residue was diluted with 2 mL of water
  11. additiontreated with 0.3 mL of AcOH with vigorous stirring
  12. stirringAfter stirring for 2 h
  13. filtrationthe solid was collected by filtration
  14. customair-dried

Sources & evidence

ORD record
ord-d4a17d1c805a4cbfa9afabf65f2dc547
Source dataset
uspto-grants-2013_03
Patent number
US08404736B2

Reaction notes

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