Diisopropylethylamine → (3s)-3-(Benzo[1,3]dioxol-5-yl)-3-((5-(2-methoxycarbonyl-ethyl)-thiophene-2-carbonyl)-amino)-propionic acid tert-butyl ester

HRID 431513Notes

Reaction equation

HRID 431513 reaction equation
[CH3:1][O:2][C:3]([CH2:5][CH2:6][C:7]1[S:11][C:10]([C:12]([OH:14])=O)=[CH:9][CH:8]=1)=[O:4].[C:15]([O:19][C:20](=[O:33])[CH2:21][C@H:22]([NH2:32])[C:23]1[CH:31]=[CH:30][C:26]2[O:27][CH2:28][O:29][C:25]=2[CH:24]=1)([CH3:18])([CH3:17])[CH3:16].[B-](F)(F)(F)F.CCOC(C(C#N)=NOC(N(C)C)=[N+](C)C)=O.C(N(C(C)C)CC)(C)C>CN(C)C=O.ClCCl>[C:15]([O:19][C:20](=[O:33])[CH2:21][C@@H:22]([C:23]1[CH:31]=[CH:30][C:26]2[O:27][CH2:28][O:29][C:25]=2[CH:24]=1)[NH:32][C:12]([C:10]1[S:11][C:7]([CH2:6][CH2:5][C:3]([O:2][CH3:1])=[O:4])=[CH:8][CH:9]=1)=[O:14])([CH3:18])([CH3:16])[CH3:17]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733286O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 108676335-(2-Methoxycarbonyl-ethyl)-thiophene-2-carboxylic acidHCID 57048399tert-butyl (3S)-3-amino-3-(1,3-dioxaindan-5-yl)propanoate

Product 1

HCID 57125533(3s)-3-(Benzo[1,3]dioxol-5-yl)-3-((5-(2-methoxycarbonyl-ethyl)-thiophene-2-carbonyl)-amino)-propionic acid tert-butyl esterYield 130%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

214 mg (1 mmol) of 5-(2-methoxycarbonyl-ethyl)-thiophene-2-carboxylic acid (example 1, step b) were dissolved in 5 ml of anhydrous dimethylformamide. 265 mg (1 mmol) of (3S)-3-amino-3-(benzo[1,3]dioxol-5-yl)-propionic acid tert-butyl ester and 328 mg (1 mmol) of TOTU were added, and 3 mmol (0.51 ml) of N,N-diisopropyl-N-ethylamine were added to keep the pH of the mixture at 7.5 to 8. The reaction mixture was stirred for 4.5 hours at room temperature. Solvents were removed under reduced pressure to give a dark brown oil. The residue was dissolved in dichloromethane and washed with saturated sodium bicarbonate solution, 10% citric acid and with water. Then the organic phase was dried with anhydrous magnesium sulfate. After filtration the solvents were removed in vacuo to give 600 mg of a brownish oil which was purified by chromatography (silica gel; ethyl acetate/heptane (1/2, v/v)). 425 mg of a resin were obtained.

Workup

  1. customSolvents were removed under reduced pressure
  2. customto give a dark brown oil
  3. washwashed with saturated sodium bicarbonate solution, 10% citric acid and with water
  4. dry with materialThen the organic phase was dried with anhydrous magnesium sulfate
  5. filtrationAfter filtration the solvents
  6. customwere removed in vacuo

Sources & evidence

ORD record
ord-a56cfa7264714c18829d69bb4f8af3b1
Source dataset
uspto-grants-2003_12
Patent number
US06660728B2

Reaction notes

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