4-Methylmorpholine → Methyl (5-chlorothiophene-2-carbonyl)alaninate

HRID 1453654Notes

Reaction equation

HRID 1453654 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[CH:4][CH:3]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.[NH2:40][CH:41]([CH3:46])[C:42]([O:44][CH3:45])=[O:43]>C1COCC1.O>[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:40][CH:41]([CH3:46])[C:42]([O:44][CH3:45])=[O:43])=[O:9])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 950485-Chloro-2-thiophenecarboxylic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 2756298Alanine, methyl ester, hydrochloride (1:1)

Product 1

HCID 60638172Methyl (5-chlorothiophene-2-carbonyl)alaninate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

3.10 g (19.1 mmol) 5-chloro-thiophene-2-carboxylic acid are combined with 4.44 ml (40 mmol) NMM and 6.42 g (20 mmol) TBTU in 50 ml THF and then stirred for 2 hours under a nitrogen atmosphere at ambient temperature. Then 2.79 g (20 mmol) methyl 2-aminopropionate-hydrochloride and 50 ml THF are added and the mixture is stirred for a further 16 hours at ambient temperature. Then the reaction mixture is poured into water, extracted with ethyl acetate, the combined organic phases are washed with sat. sodium hydrogen carbonate solution, water, 0.5-molar hydrochloric acid, water and sat. sodium chloride solution, dried over magnesium sulphate and evaporated down completely i. vac.

Workup

  1. stirringthe mixture is stirred for a further 16 hours at ambient temperature
  2. extractionextracted with ethyl acetate
  3. washthe combined organic phases are washed with sat. sodium hydrogen carbonate solution, water, 0.5-molar hydrochloric acid, water and sat. sodium chloride solution
  4. dry with materialdried over magnesium sulphate
  5. customevaporated down completely

Sources & evidence

ORD record
ord-fc6946abfb4842aea7aa6eb508ecdbef
Source dataset
uspto-grants-2009_01
Patent number
US07476663B2

Reaction notes

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