Trifluoroacetic acid → HCID 57318853, compound

HRID 976463Notes

Reaction equation

HRID 976463 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH3:13])([CH3:12])[C@@H:9]([OH:14])[C@H:8]([NH:15][C:16](=[O:32])[CH:17]([NH:24]C(=O)OC(C)(C)C)[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:7]=2[CH:33]=1)#[N:2].FC(F)(F)C(O)=O>ClCCl>[NH2:24][CH:17]([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[C:16]([NH:15][C@@H:8]1[C:7]2[CH:33]=[C:3]([C:1]#[N:2])[CH:4]=[CH:5][C:6]=2[O:11][C:10]([CH3:13])([CH3:12])[C@H:9]1[OH:14])=[O:32]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 9846627HCID 9846627, compound2×

Product 1

HCID 57318853HCID 57318853, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution containing (3S-trans)-[2-[(6-cyano-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl)amino]-2-oxo-1-phenylethyl]carbamic acid, 1,1-dimethylethyl ester (2.27 g, 5.03 mmol; the title compound of Example 1) in dichloromethane (20 mL) was added trifluoroacetic acid (5.0 mL) and the reaction mixture was stirred at room temperature for 16 hours. The volatile materials were removed under vacuum and the residue in chloroform was washed with sodium bicarbonate solution and brine. After drying over anhydrous magnesium sulfate, the solvent was evaporated and the residue was purified by flash chromatography (7.5% methanol in dichloromethane) to give two diastereomers. The faster moving material was triturated with ether to give (3S-trans)-α-amino-N-(6-cyano-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl)benzeneacetamide, isomer A (620 mg, 35.2%) as a colorless solid, mp 243°-246° C. Analysis calculated for C20H21N3O3.0.3H2O: C, 67.32; H, 6.10; N, 11.78. Found: C, 67.50; H, 5.99; N, 11.65. [α]D =-17.2° (c=1, Dimethylformamide). The slower moving material was triturated with ether to give (3S-trans)-α-amino-N-(6-cyano-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl)-benzeneacetamide, isomer B (940 mg, 53.4%) as a colorless solid, mp 109°-111° C. (with foaming). Analysis calculated for C20H21N3O3.0.45H2O: C, 66.82; H, 6.14; N, 11.69. Found: C, 67.14; H, 6.32; N, 11.14. [α]D=+29.2° (c=1, Dimethylformamide).

Workup

  1. customThe volatile materials were removed under vacuum
  2. washthe residue in chloroform was washed with sodium bicarbonate solution and brine
  3. dry with materialAfter drying over anhydrous magnesium sulfate
  4. customthe solvent was evaporated
  5. customthe residue was purified by flash chromatography (7.5% methanol in dichloromethane)
  6. customto give two diastereomers
  7. customwas triturated with ether

Sources & evidence

ORD record
ord-297b2376437b42668925e68c206c33d9
Source dataset
uspto-grants-1997_03
Patent number
US05612370

Reaction notes

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