N-Phenylglycine ethyl ester → (4aR-cis)-1,2,3,4a,5,10b-Hexahydro-5,5-dimethyl-3-oxo-1-phenyl[1]benzopyrano[3,4-b][1,4]oxazine-9-carbonitrile

HRID 356676

Reaction equation

HRID 356676 reaction equation
C(OC(=O)CNC1C=CC=CC=1)C.C[Al](C)C.CC1(C)[C@@H]2O[C@@H]2C2C=C(C#N)C=CC=2O1.[C:33]([C:35]1[CH:36]=[CH:37][C:38]2[O:43][C:42]([CH3:45])([CH3:44])[C@H:41](O)[C@@H:40]([N:47]([CH2:54][C:55]([O:57]CC)=[O:56])[C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C:39]=2[CH:60]=1)#[N:34]>ClCCCl.C(OCC)(=O)C.C(Cl)(Cl)Cl.CO>[CH3:44][C:42]1([CH3:45])[C@@H:41]2[O:56][C:55](=[O:57])[CH2:54][N:47]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C@@H:40]2[C:39]2[CH:60]=[C:35]([C:33]#[N:34])[CH:36]=[CH:37][C:38]=2[O:43]1

Participants

9

Reactant 4

HCID 75190N-Phenylglycine ethyl esterHCID 10738551(3R-trans)-[(6-cyano-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl)phenylamino]acetic acid, ethyl esterHCID 10987295(1aR,7bR)-2,2-Dimethyl-1a,7b-dihydro-2H-oxireno[2,3-c]chromene-6-carbonitrileHCID 16682925Trimethylaluminum

Product 1

HCID 67799274(4aR-cis)-1,2,3,4a,5,10b-Hexahydro-5,5-dimethyl-3-oxo-1-phenyl[1]benzopyrano[3,4-b][1,4]oxazine-9-carbonitrile

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolventHCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of N-phenylglycine ethyl ester (900 mg, 5.0 mmol) in 1,2-dichloroethane (10 mL) under argon at 20° C. was treated with trimethylaluminum (3.0 mL, 2.0M in toluene, 6.0 mmol) over 1-2 minutes. After 15 minutes, (1aR-cis)-1a,7b-dihydro-2,2-dimethyl-2H-oxireno[c][1]benzopyran-6-carbonitrile (1.0 g, 5.0 mmol, title A compound of example 3) was added at once and stirring was continued for 1.5 hours. The mixture was diluted with ethyl acetate, quenched with a few drops of water and filtered through celite to remove gelatinous aluminum salts. The filtrate was washed with 5% sodium bicarbonate, water and brine, dried over anhydrous magnesium sulfate and concentrated. The residue was triturated with warm methanol to give warm methanol to give the title product (392 mg), mp 241°-243° C. [α]D =-129.1 ° (c=0.35 CHCl3). Analysis calculated for. C20H18N2O3 ·0.14 H2O: C,71.29; H,5.47; N, 8.31. Found: C, 71.05; H, 5.30; N, 8.55.

Workup

  1. waitwas continued for 1.5 hours
  2. customquenched with a few drops of water
  3. filtrationfiltered through celite
  4. customto remove gelatinous aluminum salts
  5. washThe filtrate was washed with 5% sodium bicarbonate, water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated
  8. customThe residue was triturated with warm methanol
  9. customto give

Sources & evidence

ORD record
ord-a24d7fadbac848f990d1434e8d45cd9f
Source dataset
uspto-grants-1998_11
Patent number
US05837702

Linked notes

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