Trifluoroacetic acid → alpha-(R)-(3-(S)-((4-(6-ethoxy-benzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid

HRID 1068148노트

반응식

HRID 1068148 반응식
F[C:2]1[CH:7]=[C:6](F)[CH:5]=[CH:4][C:3]=1[C:9](=[N:19][OH:20])[CH:10]1[CH2:15][CH2:14][N:13]([C:16](=O)[CH3:17])[CH2:12][CH2:11]1.[OH-].[K+].C([C@@H]1[C@@H:29]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:28][N:27]([C@H:36]([CH:49]2[CH2:54][CH2:53][CH2:52][CH2:51][CH2:50]2)[C:37]([O:39]CC2C=CC(OC)=CC=2)=[O:38])[CH2:26]1)=O.[C:55](O)([C:57](F)(F)F)=[O:56].C1(OC)C=CC=CC=1>CCO>[CH2:55]([O:56][C:6]1[CH:5]=[CH:4][C:3]2[C:9]([CH:10]3[CH2:15][CH2:14][N:13]([CH2:16][C@@H:17]4[C@@H:29]([C:30]5[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=5)[CH2:28][N:27]([C@H:36]([CH:49]5[CH2:54][CH2:53][CH2:52][CH2:51][CH2:50]5)[C:37]([OH:39])=[O:38])[CH2:26]4)[CH2:12][CH2:11]3)=[N:19][O:20][C:2]=2[CH:7]=1)[CH3:57]

참가 물질

7

반응물 5

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 14797Potassium HydroxideHCID 53654320alpha-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid 4-methoxybenzyl esterHCID 867570241-(4-((2,4-Difluorophenyl)-hydroxyimino-methyl)piperidin-1-yl)ethanone

생성물 1

HCID 20664145alpha-(R)-(3-(S)-((4-(6-ethoxy-benzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

A solution of 1-(4-((2,4-difluorophenyl)-hydroxyimino-methyl)piperidin-1-yl)ethanone (from Step A) and KOH (45 wt. % solution) in EtOH was refluxed for 24 hours. The products were coupled with of α-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid, 4-methoxybenzyl ester (prepared above as Aldehyde 5) using a procedure analogous to that described in Example 89, Step C. The products were treated with TFA and anisole for 18 hours and concentrated under reduced pressure. The residue was purified by prep HPLC (Zorbax-RX C8 column, 30% CH3CN 15 min. and 100% CH3CN, 20 mL/min., 254 nm) to provide α-(R)-(3-(S)-((4-(6-ethoxy-benzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid: ESI-MS 546 (M+1); HPLC A: 3.01 min.; and α-(R)-(3-(S)-((4-(6-fluoro-benzo[d]isoxazol-3-yl)piperidin-1-yl)methyl)-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid: ESI-MS 520 (M+1); HPLC A: 2.88 min.

후처리

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was purified by prep HPLC (Zorbax-RX C8 column, 30% CH3CN 15 min. and 100% CH3CN, 20 mL/min., 254 nm)

출처 및 근거

ORD 기록
ord-b97bae13a51246a8b96f41e872f9bf65
출처 데이터셋
uspto-grants-2001_06
특허 번호
US06248755B1

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