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

HRID 389670Notes

Reaction equation

HRID 389670 reaction equation
[NH2:1][CH2:2][C@H:3]([NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C:4]([OH:6])=[O:5].ON1C(=O)CC[C:17]1=O.C(N=C=NC(C)C)(C)C.[Cl:32][C:33]1[S:37][C:36]([C:38]([OH:40])=O)=[CH:35][CH:34]=1.CCN(C(C)C)C(C)C.[Si](C=[N+]=[N-])(C)(C)C.Cl>C(Cl)Cl>[CH3:17][O:5][C:4](=[O:6])[C@@H:3]([NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:2][NH:1][C:38]([C:36]1[S:37][C:33]([Cl:32])=[CH:34][CH:35]=1)=[O:40]

Participants

9

Reactant 7

HCID 313Hydrochloric AcidHCID 12734DiisopropylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 81531DiisopropylethylamineHCID 950485-Chloro-2-thiophenecarboxylic acidHCID 167693TrimethylsilyldiazomethaneHCID 2755946Boc-Dap-OH

Product 1

HCID 67155290(S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(5-chlorothiophene-2-carboxamido)propanoateYield 91.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Commercially available (S)-3-amino-2-tert-butoxycarbonylamino-propionic acid (BOC-Dap-OH) (18.09 g, 88.56 mmol) was suspended in 100 ml DCM with N-hydroxy-succinimide (16.99 g, 147.61 mmol) and N,N′-diisopropylcarbodiimide (11.43 ml, 73.8 mmol), then 5-Chloro-thiophene-2-carboxylic acid (12 g, 73.8 mmol) and DIPEA (25.51 ml, 147.61 mmol) in 60 ml DCM were slowly added. The mixture was stirred at RT for 2 h, then cooled to 0° C. and TMS-diazomethane was slowly added. The reaction was stirred for 2 h at RT, HCl solution (0.5 M) was added and the organic layer was separated, washed with H2O, dried with Na2SO4, filtered and evaporated to dryness. The resulting solid was triturated 16 h with diisopropyl ether, filtered and washed with diisopropyl ether and dried under vacuum at 60° C. 24.4 g of crude product were obtained and used without further purification.

Workup

  1. temperaturecooled to 0° C.
  2. stirringThe reaction was stirred for 2 h at RT
  3. customthe organic layer was separated
  4. washwashed with H2O
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe resulting solid was triturated 16 h with diisopropyl ether
  9. filtrationfiltered
  10. washwashed with diisopropyl ether
  11. customdried under vacuum at 60° C

Sources & evidence

ORD record
ord-c93bffd3f83441cabd5fc5ba89627ea6
Source dataset
uspto-grants-2013_02
Patent number
US08378092B2

Reaction notes

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