1,2-Dichloroethane → 5-Fluoro-4-hydroxy-3-[1-(benzyloxycarbonyl)-2-piperidinecarboxamido]-pentanoic acid tert-butyl ester

HRID 1157138Notes

Reaction equation

HRID 1157138 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]1[C:17]([OH:19])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:20]([O:24][C:25](=[O:33])[CH2:26][CH:27]([NH2:32])[CH:28]([OH:31])[CH2:29][F:30])([CH3:23])([CH3:22])[CH3:21].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C1C=CN=CC=1)C.C1COCC1>[C:20]([O:24][C:25](=[O:33])[CH2:26][CH:27]([NH:32][C:17]([CH:12]1[CH2:13][CH2:14][CH2:15][CH2:16][N:11]1[C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])=[O:19])[CH:28]([OH:31])[CH2:29][F:30])([CH3:23])([CH3:21])[CH3:22]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 688345(S)-1-N-Cbz-Pipecolinic acidHCID 108566723-Amino-5-fluoro-4-hydroxy-pentanoic acid tert-butyl ester

Product 1

HCID 694637995-Fluoro-4-hydroxy-3-[1-(benzyloxycarbonyl)-2-piperidinecarboxamido]-pentanoic acid tert-butyl esterYield 89%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A stirred mixture of (S)-1-(benzyloxy carbonyl)-2-piperidinecarboxylic acid (4.82 g, 18.31 mmol), 3-amino-5-fluoro-4-hydroxy-pentanoic acid tert-butyl ester (3.99 g, 19.25 mmol), HOBt (2.72 g, 20.13 mmol), DMAP (2.57 g, 21.04 mmol) and anhydrous THF (60 ml) was cooled to 0° C. before EDC (3.86 g, 20.13 mmol) was added. The mixture was allowed to warm to room temperature over 16 hrs before being concentrated under reduced pressure. The residue was purified by flash chromatography (60% ethyl acetate in hexane) to afford the sub-title compound as a white foam (7.3754 g, 72%): 1H NMR (400 MHz, CDCl3) δ 1.31-1.80 (14H, m), 2.20-2.38 (1H, m), 2.49-3.07 (3H, m), 3.11-3.70 (1H, m), 3.80-4.58 (4H, m), 4.70-5.28 (1H, m), 6.58-7.05 (1H, m), 7.23-7.48 (5H, m).

Workup

  1. additionwas added
  2. concentrationbefore being concentrated under reduced pressure
  3. customThe residue was purified by flash chromatography (60% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-1bb97e8f24124b0593896e78f2356320
Source dataset
uspto-grants-2010_10
Patent number
US07807659B2

Reaction notes

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