Diisopropylethylamine → 5-Fluoro-4-hydroxy-3-[1-(2-phenyl-thiazole-4-carbonyl)-2-piperidine-carboxamido]-pentanoic acid tert-butyl ester

HRID 1157140Notes

Reaction equation

HRID 1157140 reaction equation
[C:1]([O:5][C:6](=[O:22])[CH2:7][CH:8]([NH:13][C:14]([CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][NH:17]1)=[O:15])[CH:9]([OH:12])[CH2:10][F:11])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[C:32]1([C:38]2[S:39][CH:40]=[C:41]([C:43](O)=[O:44])[N:42]=2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:22])[CH2:7][CH:8]([NH:13][C:14]([CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][N:17]1[C:43]([C:41]1[N:42]=[C:38]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[S:39][CH:40]=1)=[O:44])=[O:15])[CH:9]([OH:12])[CH2:10][F:11])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1389282-Phenyl-4-carboxythiazoleHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 694642585-Fluoro-4-hydroxy-3-[2-piperidinecarboxamido]-pentanoic acid tert-butyl ester

Product 1

HCID 694642535-Fluoro-4-hydroxy-3-[1-(2-phenyl-thiazole-4-carbonyl)-2-piperidine-carboxamido]-pentanoic acid tert-butyl esterYield 56.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A stirred solution of [3S/R,4S/R,(2S)]-5-fluoro-4-hydroxy-3-[2-piperidinecarboxamido]-pentanoic acid tert-butyl ester (520 mg, 1.63 mmol), in DMF (9.7 ml) at room temperature was treated with DIPEA (311 μl, 1.80 mmol). The resulting mixture was allowed to stir for 30 min before being treated with 2-phenyl-thiazole-4-carboxylic acid (335 mg, 1.63 mmol) and TBTU (524 mg, 1.63 mmol). The mixture was stirred at room temperature for 16 hr and then diluted with ethyl acetate. The resulting solution was washed with 2 N HCl, saturated aq. NaHCO3, saturated aq. NaCl, dried (Na2SO4), filtered and concentrated to reveal an oil. The residue was purified by flash chromatography (60% ethyl acetate in hexane) to afford the sub-title compound as a colorless oil (463 mg, 56%): 1H NMR (400 MHz, CDCl3) δ 1.10-1.85 (15H, m), 2.22-2.89 (3H, m), 3.09-4.78 (6H, m), 5.20-5.43 (1H, m), 7.40-7.56 (3H, m), 7.81-8.11 (3H, m).

Workup

  1. stirringThe mixture was stirred at room temperature for 16 hr
  2. washThe resulting solution was washed with 2 N HCl, saturated aq. NaHCO3, saturated aq. NaCl
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (60% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-f55d3f467e1e4f3da55f9b01b661384a
Source dataset
uspto-grants-2010_10
Patent number
US07807659B2

Reaction notes

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