Diisopropylethylamine → (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(5-chlorothiophene-2-carboxamido)propanoate

HRID 389645Notes

Reaction equation

HRID 389645 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[B-](F)(F)(F)F.CCOC(C(C#N)=NOC(N(C)C)=[N+](C)C)=O.Cl.[CH3:42][O:43][C:44](=[O:56])[C@@H:45]([NH:48][C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:46][NH2:47]>C(Cl)Cl>[CH3:42][O:43][C:44](=[O:56])[C@@H:45]([NH:48][C:49]([O:51][C:52]([CH3:54])([CH3:53])[CH3:55])=[O:50])[CH2:46][NH:47][C:7]([C:5]1[S:6][C:2]([Cl:1])=[CH:3][CH:4]=1)=[O:9]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 950485-Chloro-2-thiophenecarboxylic acidHCID 2733286O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 71607207Methyl 3-amino-N-(tert-butoxycarbonyl)-L-alaninate--hydrogen chloride (1/1)

Product 1

HCID 67155290(S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(5-chlorothiophene-2-carboxamido)propanoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-Chloro-thiophene-2-carboxylic acid (16.26 g, 0.1 mol) in 500 ml DCM was stirred with DIPEA (51.04 ml, 0.3 mol) and TOTU (32.8 g, 0.1 mmol) at RT for 5 min. Commercially available (S)-3-amino-2-tert-butoxycarbonylamino-propionic acid methyl ester hydrochloride (25.4 g, 0.1 mol) were added and the reaction mixture was stirred at RT overnight and then evaporated. The resulting solid was suspended in 400 ml DCM and washed subsequently with sat. aq NaHCO3, 1N HCl and brine. The organic layer was dried with MgSO4, filtered and evaporated. The crude material was triturated with DCM and the solid filtered off. One obtained 18.4 g white, amorphous solid which was used in the next step without further purification.

Workup

  1. customevaporated
  2. washwashed subsequently with sat. aq NaHCO3, 1N HCl and brine
  3. dry with materialThe organic layer was dried with MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude material was triturated with DCM
  7. filtrationthe solid filtered off
  8. customOne obtained 18.4 g white
  9. customamorphous solid which was used in the next step without further purification

Sources & evidence

ORD record
ord-76076d44f4b14dc4935e4b6717755c48
Source dataset
uspto-grants-2013_02
Patent number
US08378092B2

Reaction notes

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