1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl (3R)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)hex-5-enoate

HRID 1700971Notes

Reaction equation

HRID 1700971 reaction equation
CN(CCCN=C=NCC)C.[C:12]([O:16][C:17](=[O:26])[CH2:18][C@@H:19]([CH2:23][CH:24]=[CH2:25])[C:20]([OH:22])=O)([CH3:15])([CH3:14])[CH3:13].ON1C2N=CC=CC=2N=N1.Cl.[NH2:38][C@@H:39]([C:51]([CH3:54])([CH3:53])[CH3:52])[C:40]([NH:42][C@@H:43]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[CH3:44])=[O:41].C(N(C(C)C)CC)(C)C>CN(C)C=O>[CH3:53][C:51]([CH3:52])([CH3:54])[C@H:39]([NH:38][C:20]([C@H:19]([CH2:23][CH:24]=[CH2:25])[CH2:18][C:17]([O:16][C:12]([CH3:13])([CH3:14])[CH3:15])=[O:26])=[O:22])[C:40]([NH:42][C@@H:43]([C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)[CH3:44])=[O:41]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 10560578(R)-2-(2-(tert-butoxy)-2-oxoethyl)pent-4-enoic acidHCID 69991487(2S)-amino-3,3-dimethyl-N-[(1R)-1-phenylethyl]butanamide hydrochloride

Product 1

HCID 54508002tert-butyl (3R)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)hex-5-enoateYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(Dimethylaminopropyl)-N′-ethylcarbodiimide (4.21 g, 22.0 mmol) was added to a stirred mixture of (2R)-2-[2-(tert-butoxy)-2-oxoethyl]pent-4-enoic acid (A. L. Castelhano, S. L. Bender, J. G. Deal, S. Homer, T. J. Liak, Z. Yuan, World Patent WO96/16027 (1996)) (3.80 g, 17.8 mmol) and 1-hydroxy-7-azabenzotriazole (2.49 g, 18.3 mmol) in anhydrous dimethylformamide (60 mL) under nitrogen at 4° C. After 1 h, (2S)-amino-3,3-dimethyl-N-[(1R)-1-phenylethyl]butanamide hydrochloride (Preparation 1)(5.10 g, 18.8 mmol) was added, followed by diisopropylethylamine (2.42 g, 19.2 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 (400 mL) and water (400 mL). The aqueous layer was saturated with sodium bicarbonate and extracted with ethyl acetate (2×100 mL). The combined organic solutions were concentrated under reduced pressure, the residue was dissolved in ether (500 mL) and washed with water (3×200 mL), dried (MgSO4), and concentrated under reduced pressure. The residue was triturated with pentane, filtered and dried to give tert-butyl (3R)-3-({[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)hex-5-enoate (6.70 g, 88%), as a colourless solid.

Workup

  1. customat 4° C
  2. waitAfter another 30 min
  3. waitAfter 17 h at room temperature
  4. concentrationthe mixture was concentrated under reduced pressure
  5. custompartitioned between ethyl acetate (400 mL) and water (400 mL)
  6. extractionextracted with ethyl acetate (2×100 mL)
  7. concentrationThe combined organic solutions were concentrated under reduced pressure
  8. dissolutionthe residue was dissolved in ether (500 mL)
  9. washwashed with water (3×200 mL)
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was triturated with pentane
  13. filtrationfiltered
  14. customdried

Sources & evidence

ORD record
ord-310c5768fd1b45baab2a021d8e5a5457
Source dataset
uspto-grants-2002_02
Patent number
US06350907B1

Reaction notes

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