(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

반응식

HRID 1457722 반응식
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]

참가 물질

6

반응물 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

생성물 1

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

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-546be415cb4941c38c67f706a969fee6
출처 데이터셋
uspto-grants-1998_12
특허 번호
US05849736

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