(S)-[(2R,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol → 3-(4-Cyanophenyl)isoxazolin-5-ylacetic acid

HRID 1457722

Reaction equation

HRID 1457722 reaction equation
C[C@H:2]([NH:11]C)[C@H](O)C1C=CC=CC=1.[C:13]1([CH:19]([CH2:21]O)[NH2:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.N[CH:24]([CH2:27][O:28]C)[CH2:25][OH:26].C[O:31]C1C=CC2N=CC=C([C@H](O)[C@@H]3N4C[C@H](C=C)C(CC4)C3)C=2C=1.C[C@H](NC)[C@@H](O)C1C=CC=CC=1>>[C:2]([C:16]1[CH:15]=[CH:14][C:13]([C:19]2[CH2:21][CH:27]([CH2:24][C:25]([OH:26])=[O:31])[O:28][N:20]=2)=[CH:18][CH:17]=1)#[N:11]

Participants

6

Reactant 5

HCID 5953(S)-[(2R,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanolHCID 7028PseudoephedrineHCID 9294EphedrineHCID 924662-Amino-2-phenylethanolHCID 141514112-Amino-3-methoxypropan-1-OL

Product 1

HCID 110425463-(4-Cyanophenyl)isoxazolin-5-ylacetic acid

Procedure

3-(4-Cyanophenyl)isoxazolin-5(S)-ylacetic acid (127 g, 0.55 moles) and (+)-cinchonidine (180.37 g, 0.55 mol) were added to acetone (2.0 L) and stirred at ambien temperature for at least 1.5 hrs. The resulting precipitate (169.21 g) was collected by filtration. The precipitate was dissolved in hot acetone (4.0 L) while stirring. After complete dissolution, the solution was allowed to stand overnight. The crystals formed were collected by filtration and recrystallized with acetone again to yield the 3-(4-cyanophenyl)isoxazolin-5(S)-ylacetic acid/(+)-cinchonidine salt in 33% overall yield and >99% diastereomeric excess. The 3-(4-cyanophenyl)isoxazolin-5(S)-ylacetic acid was liberated from its cinchonidine salt complex by suspending the salt in ethereal HCL (1N), filtering the solid after equilibration and evaporating the ether solution to provide the solid 3-(4-cyanophenyl)isoxazolin-5(S)-ylacetic acid. The R-isomer could be obtained from the mother liquor. Other chiral bases used include ephedrine, 2-phenylglycinol, 2-amino-3-methoxy-1-propanol, quinidine and pseudoephedrine.

Workup

  1. customThe R-isomer could be obtained from the mother liquor

Sources & evidence

ORD record
ord-546be415cb4941c38c67f706a969fee6
Source dataset
uspto-grants-1998_12
Patent number
US05849736

Linked notes

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