Diisopropylethylamine → methyl (2S,3R)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-2-ethoxy-hex-5-enoate

HRID 1700980Notes

Reaction equation

HRID 1700980 reaction equation
Cl.CN(CCCN=C=NCC)C.[C:13]([C@H:16]([CH:25]=[CH:26][CH3:27])[C@H:17]([O:22][CH2:23][CH3:24])[C:18]([O:20][CH3:21])=[O:19])([OH:15])=O.ON1C2N=CC=CC=2N=N1.Cl.[NH2:39][C@@H:40]([C:52]([CH3:55])([CH3:54])[CH3:53])[C:41]([NH:43][C@@H:44]([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)[CH3:45])=[O:42].C(N(C(C)C)CC)(C)C>CN(C)C=O>[CH3:54][C:52]([CH3:53])([CH3:55])[C@H:40]([NH:39][C:13]([C@H:16]([CH2:25][CH:26]=[CH2:27])[C@H:17]([O:22][CH2:23][CH3:24])[C:18]([O:20][CH3:21])=[O:19])=[O:15])[C:41]([NH:43][C@@H:44]([C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1)[CH3:45])=[O:42]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57104305methyl (2S, 3R)-3-carboxy-2-ethoxy-hex-4-enoateHCID 69991487(2S)-amino-3,3-dimethyl-N-[(1R)-1-phenylethyl]butanamide hydrochloride

Product 1

HCID 86757820methyl (2S,3R)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-2-ethoxy-hex-5-enoateYield 43.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (214 mg, 1.12 mmol) was added to a stirred mixture of methyl (2S, 3R)-3-carboxy-2-ethoxy-hex-4-enoate (Preparation 7) (210 mg, 0.97 mmol) and 1-hydroxy-7-azabenzotriazole (139 mg, 1.02 mmol) in anhydrous dimethylformamide (4 mL) under nitrogen at 0° C. After 1 h, (2S)-amino-3,3-dimethyl-N-[(1R)-1-phenylethyl]butanamide hydrochloride (Preparation 1)(276 mg, 1.02 mmol) was added, followed by diisopropylethylamine (0.18 μL, 1.02 mmol). After another 30 min, the mixture was allowed to warm to room temperature. After 17 h at room temperature, the mixture was concentrated under reduced pressure, and partitioned between ethyl acetate (50 mL) and water (50 mL). The aqueous layer was saturated with sodium bicarbonate and extracted with ethyl acetate (2×20 mL). The combined organic solutions were concentrated under reduced pressure, dissolved in ether (50 mL), washed with water (3×20 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by flash chromatography (eluting with hexane:ethyl acetate=60:40) to give methyl (2S,3R)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-2-ethoxy-hex-5-enoate (181 mg, 43%), as a colourless solid (single diastereomer by 1H NMR).

Workup

  1. waitAfter another 30 min
  2. waitAfter 17 h at room temperature
  3. concentrationthe mixture was concentrated under reduced pressure
  4. custompartitioned between ethyl acetate (50 mL) and water (50 mL)
  5. extractionextracted with ethyl acetate (2×20 mL)
  6. concentrationThe combined organic solutions were concentrated under reduced pressure
  7. dissolutiondissolved in ether (50 mL)
  8. washwashed with water (3×20 mL)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by flash chromatography (eluting with hexane:ethyl acetate=60:40)

Sources & evidence

ORD record
ord-d15a91e405ea4f5283885f61895dd781
Source dataset
uspto-grants-2002_02
Patent number
US06350907B1

Reaction notes

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