1,2-Dichloroethane → 3-[2-(2-carbazol-9-yl-2-oxo-ethyl)-pentanoylamino]-5-fluoro-4-hydroxy-pentanoic Acid Tert-Butyl Ester

HRID 254799Notes

Reaction equation

HRID 254799 reaction equation
[CH:1]1[C:13]2[N:12]([C:14](=[O:23])[CH2:15][C@@H:16]([CH2:20][CH2:21][CH3:22])[C:17](O)=[O:18])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[C:24]([O:28][C:29](=[O:37])[CH2:30][CH:31]([NH2:36])[CH:32]([OH:35])[CH2:33][F:34])([CH3:27])([CH3:26])[CH3:25].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C1C=CN=CC=1)C.C1COCC1>[C:24]([O:28][C:29](=[O:37])[CH2:30][CH:31]([NH:36][C:17](=[O:18])[CH:16]([CH2:15][C:14]([N:12]1[C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:5]2[C:13]1=[CH:1][CH:2]=[CH:3][CH:4]=2)=[O:23])[CH2:20][CH2:21][CH3:22])[CH:32]([OH:35])[CH2:33][F:34])([CH3:27])([CH3:25])[CH3:26]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 108566723-Amino-5-fluoro-4-hydroxy-pentanoic acid tert-butyl esterHCID 57418779(2R)-2-(2-carbazol-9-yl-2-oxo-ethyl)-pentanoic acid

Product 1

HCID 668783273-[2-(2-carbazol-9-yl-2-oxo-ethyl)-pentanoylamino]-5-fluoro-4-hydroxy-pentanoic Acid Tert-Butyl EsterYield 53%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A stirred mixture of (2R)-2-(2-carbazol-9-yl-2-oxo-ethyl)-pentanoic acid (2.94 g, 9.50 mmol), 3-amino-5-fluoro-4-hydroxy-pentanoic acid tert-butyl ester (2.07 g, 9.99 mmol), HOBT (1.41 g, 10.43 mmol), DMAP (1.34 g, 10.97 mmol) and anhydrous THF (40 mL) was cooled to 0° C. then EDC (2.00 g, 10.43 mmol) was added. The mixture was allowed to warm to room temperature during 16 h then concentrated under reduced pressure. The residue purified by flash chromatography (33% EtOAc in 40/60 hexanes) to give the sub-title compound (2.51 g, 53%) as a foam: 1H NMR (400 MHz, CDCl3) δ 0.90-1.03 (3H, m), 1.20-1.90 (13H, m), 2.50-3.00 (3H, m), 3.12-3.26 (1H, m), 3.59-3.80 (2H, m), 4.00-4.68 (3H, m), 6.53-6.89 (1H, m), 7.30-7.52 (4H, m), 7.95-8.05 (2H, m), 8.15-8.26 (2H, m) 19F NMR (376 MHz, CDCl3) δ −229.10, −229.34, −230.95, −231.09.

Workup

  1. temperatureto warm to room temperature during 16 h
  2. concentrationthen concentrated under reduced pressure
  3. customThe residue purified by flash chromatography (33% EtOAc in 40/60 hexanes)

Sources & evidence

ORD record
ord-295797897b8d4ca68f04cef1fb6edb27
Source dataset
uspto-grants-2011_01
Patent number
US07875712B2

Reaction notes

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