Dicyclohexylcarbodiimide → 6-Cyano-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl-alpha-hydroxybenzeneacetamide

HRID 129179Notes

Reaction equation

HRID 129179 reaction equation
N[C@@H:2]1[C:7]2[CH:8]=[C:9]([C:12]#[N:13])[CH:10]=[CH:11][C:6]=2[O:5][C:4]([CH3:15])([CH3:14])[C@H:3]1[OH:16].[CH:17]1[CH:22]=[CH:21][C:20]([C@@H:23]([OH:27])[C:24](O)=[O:25])=[CH:19][CH:18]=1.O.OC1C2N=N[NH:35]C=2C=CC=1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O>[C:12]([C:9]1[CH:10]=[CH:11][C:6]2[O:5][C:4]([CH3:15])([CH3:14])[C:3]([OH:16])=[C:2]([C:21]3[CH2:22][CH2:17][CH:18]=[CH:19][C:20]=3[CH:23]([OH:27])[C:24]([NH2:35])=[O:25])[C:7]=2[CH:8]=1)#[N:13]

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 11914(-)-Mandelic acidHCID 10943936(3S,4R)-4-amino-3-hydroxy-2,2-dimethyl-chroman-6-carbonitrileHCID 178526939HCID 178526939, compound

Product 1

HCID 867491036-Cyano-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl-alpha-hydroxybenzeneacetamideYield 32.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (trans)-4-amino-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (prepared according to Evans et al., J. Med. Chem., 1983, 26, p. 1582 and J. Med. Chem., 1986, 29, p. 2194) (1.64 g, 7.5 mmol), R(-)-mandelic acid (1.14 g, 7.5 mmol), hydroxybenzotriazole hydrate (1.0 g, 7.5 mmol) in dimethylformamide (15 ml) at 0° C. was added dicyclohexylcarbodiimide (1.55 g, 7.5 mmol) at room temperature. The reaction mixture was allowed to stir at room temperature for 20 hours and then cooled in an ice bath. The solid was removed by filtration and the filtrate was concentrated in vacuo. The residue was dissolved in 5% methanol in chloroform and washed wish 1N sodium hydroxide, 1N hydrochloric acid, brine followed by drying over anhydrous magnesium sulfate. After removing drying agent the solvent was removed in vacuo. The residue was crystallized from ethanol to give the title compound (0.85 g) as a white solid, m.p. 235°-237° C.: [αD ]25 =-94.9° (c=1, MeOH); 1H NMR (DMSO-d6) δ8.45 (d, J=8.0 Hz, 1H), 7.5 (m, 4H), 7.3 (m, 2H), 7.0 (s, 1H), 6.88 (d, J=8.0 Hz, 1H), 6.2 (s, 1H), 5.57 (d, J=5.0 Hz, 1H), 5.0 (s, 1H), 4.76 (t, J=9.0 Hz, 1H), 3.75 (dd, J=4.0 & 5.0 Hz, 1H), 1.40 (s, 3H), 1.15 (s, 3H).

Workup

  1. temperaturecooled in an ice bath
  2. customThe solid was removed by filtration
  3. concentrationthe filtrate was concentrated in vacuo
  4. dissolutionThe residue was dissolved in 5% methanol in chloroform
  5. washwashed
  6. dry with materialby drying over anhydrous magnesium sulfate
  7. customAfter removing
  8. customdrying agent the solvent
  9. customwas removed in vacuo
  10. customThe residue was crystallized from ethanol

Sources & evidence

ORD record
ord-967ecfea0f8248e283e85dc4b0cb4ce8
Source dataset
uspto-grants-1995_11
Patent number
US05466817

Reaction notes

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