Trifluoroacetic acid → HCID 178462112, compound

HRID 2229932Notes

Reaction equation

HRID 2229932 reaction equation
FC(F)(F)C(O)=O.C(O[C:13]([NH:15][C@@H:16]([C:18]([NH:20][C@H:21]1[CH2:25][C:24](=[O:26])[O:23][C@@H:22]1[O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:19])[CH3:17])=[O:14])(C)(C)C.C(N(C(C)C)CC)(C)C.[C:44]1([CH2:50][CH2:51][CH2:52][C:53]2[N:54]=[C:55](C(O)=O)[NH:56][CH:57]=2)[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.Cl.CN(C)CCCN=C=NCC.OC1C2N=NNC=2C=CC=1>ClCCl.CN(C=O)C.[Cl-].[Na+].O>[C:44]1([CH2:50][CH2:51][CH2:52][C:53]2[N:54]=[C:55]([C:13]([NH:15][C@@H:16]([C:18]([NH:20][C@H:21]3[CH2:25][C:24](=[O:26])[O:23][C@@H:22]3[O:27][CH2:28][C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[O:19])[CH3:17])=[O:14])[NH:56][CH:57]=2)[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1

Participants

10

Reactant 6

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67674898(2R,S,3S) N2-Tert-butoxycarbonyl-N-(tetrahydro-2-benzyloxy-5-oxo-3-furanyl)-L-alaninamideHCID 178418300HCID 178418300, compoundHCID 178524887HCID 178524887, compound

Product 1

HCID 178462112HCID 178462112, compoundYield 76.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

Trifluoroacetic acid (7 ml) was added to a solution of (2R,S,3S) N2-tert-butoxycarbonyl-N-(tetrahydro-2-benzyloxy-5-oxo-3-furanyl)-L-alaninamide (14) (1.00 g, 2.64 mmol) in dichloromethane (7 ml) at 0° C. The mixture was stirred at 0° C. for 75 min. The mixture was concentrated, and the residue treated with diethyl ether then the ether was removed under vacuum. This procedure was repeated twice to yield a pale yellow glass. The solid was dissolved in DMF (20 ml). Diisopropylethylamine (1.38 ml, 7.92 mmol) followed by 4-(3-phenylpropyl) imidazole-2-carboxylic acid (13d) (0.67 g, 290 mmol), 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (0.56 g, 2.90 mmol) and hydroxybenzotriazole (0.71 g, 5.28 mmol) were then added to this solution. The mixture was stirred at room temperature for 20 h then poured into brine. The mixture was extracted with ethyl acetate (3×50 ml). The combined organic extracts were washed with saturated aqueous sodium bicarbonate (2×100 ml) then brine (2×100 ml), dried (MgSO4), filtered and concentrated. The residue was purified by column chromatography (ethyl acetate) to afford 0.99 g (76%) of 17d as a mixture of diastereomers: IR (KBr) 3293, 3064, 2937, 1793, 1650, 1530, 1451, 1446, 1119; 1H NMR (CDCl3) δ7.96 (brm), 7.62 (brd), 7.36-7.10 (10H, m), 6.88 (s), 6.86 (s), 5.53 (d, J=5.2), 5.48 (s), 4.87-4.52 (4H, m), 3.11-2.38 (2H, m), 2.65 (4H, m), 1.99 (2H, m), 1.47 (d, J=6.9), 1.46 (d, J=7.0).

Workup

  1. concentrationThe mixture was concentrated
  2. additionthe residue treated with diethyl ether
  3. customthe ether was removed under vacuum
  4. customto yield a pale yellow glass
  5. additionwere then added to this solution
  6. stirringThe mixture was stirred at room temperature for 20 h
  7. extractionThe mixture was extracted with ethyl acetate (3×50 ml)
  8. washThe combined organic extracts were washed with saturated aqueous sodium bicarbonate (2×100 ml)
  9. dry with materialbrine (2×100 ml), dried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-dda32a393b334a7f9702f180c1d3b42f
Source dataset
uspto-grants-2002_07
Patent number
US06420522B1

Reaction notes

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