Diisopropylethylamine → (2R)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-N-[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]pent-4-enamide

HRID 1700986Notes

Reaction equation

HRID 1700986 reaction equation
[C:1]([C@@H:4]([C@H:8]1[C:12](=[O:13])[O:11][C:10]([CH3:15])([CH3:14])[O:9]1)[CH2:5][CH:6]=[CH2:7])([OH:3])=O.ON1C2N=CC=CC=2N=N1.Cl.CN(CCCN=C=NCC)C.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>ClCCl>[CH3:14][C:10]1([CH3:15])[O:9][C@@H:8]([C@@H:4]([CH2:5][CH:6]=[CH2:7])[C:1]([NH:39][C@H:40]([C:41]([NH:43][C@@H:44]([C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=2)[CH3:45])=[O:42])[C:52]([CH3:53])([CH3:54])[CH3:55])=[O:3])[C:12](=[O:13])[O:11]1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59875758(4S)-4-[(1R)-1-carboxy-but-3-enyl]-2,2-dimethyl-1,3-dioxolan-5-oneHCID 69991487(2S)-amino-3,3-dimethyl-N-[(1R)-1-phenylethyl]butanamide hydrochloride

Product 1

HCID 57042918(2R)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-N-[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]pent-4-enamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A portion of the crude (4S)-4-[(1R)-1-carboxy-but-3-enyl]-2,2-dimethyl-1,3-dioxolan-5-one from b) above (calculated from the NMR to contain 1.54 g, 7.19 mmol) and 1-hydroxy-7-aza-1H-1,2,3-benzotriazole (1.09 g, 7.55 mmol) in anhydrous dichloromethane (30 mL) were mixed and cooled to 0° C. under nitrogen. N-(Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.60 g, 8.27 mmol) was added, and the mixture was stirred for 1.5 h at 0° C. (2S)-Amino-3,3-dimethyl-N-[(1R)-1-phenylethyl]butanamide hydrochloride (Preparation 1)(2.15 g, 7.55 mmol) was added, followed by diisopropylethylamine (1.37 mL, 7.55 mmol). After another 45 min, the mixture was allowed to warm to room temperature. After 3 h at room temperature, the mixture was partitioned between ethyl acetate (200 mL) and pH 7 aqueous phosphate buffer (100 mL). The organic layer was washed with sodium bicarbonate, brine, dried (Na2SO4), and concentrated under reduced pressure. The resulting foam crystallised upon addition of ether, and the white solid (1.89 g) was filtered off. Recystallisation from ethyl acetate/hexane gave (2R)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-N-[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]pent-4-enamide as a white solid (1.30 g, 42%, as a single diastereomer).

Workup

  1. additionwere mixed
  2. additionwas added
  3. temperatureto warm to room temperature
  4. waitAfter 3 h at room temperature
  5. customthe mixture was partitioned between ethyl acetate (200 mL) and pH 7 aqueous phosphate buffer (100 mL)
  6. washThe organic layer was washed with sodium bicarbonate, brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting foam crystallised upon addition of ether
  10. filtrationthe white solid (1.89 g) was filtered off

Sources & evidence

ORD record
ord-e10136805d774e71abdcce7ecf886294
Source dataset
uspto-grants-2002_02
Patent number
US06350907B1

Reaction notes

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