5-Ethyl-2-thiophenecarboxaldehyde → 3-[(5-Ethyl-thiophen-2-ylmethyl)-amino]-propionic acid tert-butyl ester

HRID 1045043Notes

Reaction equation

HRID 1045043 reaction equation
[CH2:1]([C:3]1[S:7][C:6]([CH:8]=O)=[CH:5][CH:4]=1)[CH3:2].Cl.[C:11]([O:15][C:16](=[O:20])[CH2:17][CH2:18][NH2:19])([CH3:14])([CH3:13])[CH3:12].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:11]([O:15][C:16](=[O:20])[CH2:17][CH2:18][NH:19][CH2:8][C:6]1[S:7][C:3]([CH2:1][CH3:2])=[CH:4][CH:5]=1)([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 1698305-Ethyl-2-thiophenecarboxaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 16218890Tert-butyl 3-aminopropanoate hydrochloride

Product 1

HCID 671819993-[(5-Ethyl-thiophen-2-ylmethyl)-amino]-propionic acid tert-butyl esterYield 32.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-ethyl-thiophene-2-carboxaldehyde (14.25 g, 101.6 mmol) and 3-amino-propionic acid tert-butyl ester hydrochloride (22.2 g, 122 mmol) in DCM was stirred for 3 hr at RT. Sodium triacetoxyborohydride (30.1 g, 142.2 mmol) was added in portions and the reaction was stirred for 2 h, at which point TLC indicated the completion of the reaction. To the reaction mixture was added a saturated aq solution of sodium bicarbonate, and then the phases were separated. The aqueous layer was extracted with DCM two times. The combined organic extracts were dried over sodium sulfate, concentrated under vacuum and the resulting material was purified on a silica gel column (eluent: hexanes→2% hexanes in EtOAc→5% hexanes in EtOAc→10% hexanes in EtOAc→20% hexanes in EtOAc→50% hexanes in EtOAc) to give 3-[(5-ethyl-thiophen-2-ylmethyl)-amino]-propionic acid tert-butyl ester (8.91 g, 32.6% yield).

Workup

  1. stirringthe reaction was stirred for 2 h, at which point TLC
  2. customthe completion of the reaction
  3. customthe phases were separated
  4. extractionThe aqueous layer was extracted with DCM two times
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customthe resulting material was purified on a silica gel column (eluent: hexanes→2% hexanes in EtOAc→5% hexanes in EtOAc→10% hexanes in EtOAc→20% hexanes in EtOAc→50% hexanes in EtOAc)

Sources & evidence

ORD record
ord-16a4ed69a7b8428195cf629e0fff16a6
Source dataset
uspto-grants-2013_10
Patent number
US08563742B2

Reaction notes

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