(3S,4R)-4-amino-3-hydroxy-2,2-dimethyl-chroman-6-carbonitrile → HCID 57242264, compound

HRID 1492449Notes

Reaction equation

HRID 1492449 reaction equation
[NH2:1][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].[O:17]1[C:21]([C:22]2[CH:23]=[C:24]([NH:28][C:29](=O)[O:30]C3C=CC([N+]([O-])=O)=CC=3)[CH:25]=[CH:26][CH:27]=2)=[N:20][CH:19]=[N:18]1>C(#N)C.CN(C)C=O>[C:12]([C:9]1[CH:10]=[CH:11][C:6]2[O:5][C:4]([CH3:14])([CH3:15])[C@@H:3]([OH:16])[C@H:2]([NH:1][C:29]([NH:28][C:24]3[CH:25]=[CH:26][CH:27]=[C:22]([C:21]4[O:17][N:18]=[CH:19][N:20]=4)[CH:23]=3)=[O:30])[C:7]=2[CH:8]=1)#[N:13]

Participants

5

Reactant 2

HCID 10943936(3S,4R)-4-amino-3-hydroxy-2,2-dimethyl-chroman-6-carbonitrileHCID 57265169HCID 57265169, compound

Product 1

HCID 57242264HCID 57242264, compoundYield 88.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (3S-trans)-4-amino-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (0.65 g, 0.0030 mol, from example 1, part B) and [3-(1,2,4-oxadiazol-5-yl)]phenylcarbamic acid, 4-nitrophenyl ester (1.08 g, 0.0033 mol) in acetonitrile (25 mL) and dimethylformamide (20 mL) was stirred at 80° C. for one hour. The reaction mixture was concentrated in vacuo and the residue, diluted with ethyl acetate, was washed with 10% citric acid and water. The organic layer was dried over MgSO4 and concentrated in vacuo. The product was purified by flash chromatography (Sorbisol C 60 flash silica gel, 400 mL) and eluted with Hexane/EtOAc (2:1) and Hexane/EtOAc (1:1). The solvent was removed in vacuo, to give a solid that was triturated with anhydrous ether and dried in vacuo to yield 1.08 g of the title compound, m.p. 168°-170° C. TLC, silica gel, EtOAc/Hexane(2:l), Rf =0.42. 1H-NMR (DMSO-d6) δ9.1 (s, 1H), 9.0 (s, 1H), 8.5 (s, 1H), 7.5 (m, 4H), 7.0 (d, J=8.8 Hz 1H), 6.8 (d, J=8.8 Hz, 1H), 5.7 (d, J=5.9 Hz, 1H), 4.7 (t, J=8.8 Hz, 1H), 3.7 (dd, J=5.9 & 3.5 Hz, 1H), 3.4 (s, 1H), 1.5 (s, 3H), 1.2 (s, 3H); 13C-NMR (DMSO-d6) δ174.8, 158.6, 156.3, 155.7, 141.4, 132.6, 132.5, 130.0, 125.9, 123.7, 122.3, 120.6, 119.1, 117.9, 116.7, 102.7,l 80.4, 71.3, 49.5, 26.6, 18.9; IR (KBr) 2228, 1667, 1574, 1551, 1489 cm-1.M.S. (M+H)+ at 406, M.W. 405; [α]D =-55.20° (c=0.86 DMSO).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionthe residue, diluted with ethyl acetate
  3. washwas washed with 10% citric acid and water
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe product was purified by flash chromatography (Sorbisol C 60 flash silica gel, 400 mL)
  7. washeluted with Hexane/EtOAc (2:1) and Hexane/EtOAc (1:1)
  8. customThe solvent was removed in vacuo
  9. customto give a solid
  10. customthat was triturated with anhydrous ether
  11. customdried in vacuo

Sources & evidence

ORD record
ord-501bf5c648fc4a239b00742880c10ab7
Source dataset
uspto-grants-1994_12
Patent number
US05374643

Reaction notes

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