ethyl 2-[(3R)-piperidin-3-yl]acetate → ethyl 2-((3R)-1-(2-hydroxy-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)ethyl)piperidin-3-yl)acetate

HRID 1506354Notes

Reaction equation

[O:1]1[CH2:3][CH:2]1[C:4]1[CH:5]=[C:6]2[C:29](=[CH:30][CH:31]=1)[C:10]1=[N:11][O:12][C:13]([C:14]3[C:18]([C:19]([F:22])([F:21])[F:20])=[C:17]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[O:16][N:15]=3)=[C:9]1[CH2:8][CH2:7]2.[NH:32]1[CH2:37][CH2:36][CH2:35][C@H:34]([CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH2:33]1>CC(O)C>[OH:1][CH:2]([C:4]1[CH:5]=[C:6]2[C:29](=[CH:30][CH:31]=1)[C:10]1=[N:11][O:12][C:13]([C:14]3[C:18]([C:19]([F:22])([F:20])[F:21])=[C:17]([C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)[O:16][N:15]=3)=[C:9]1[CH2:8][CH2:7]2)[CH2:3][N:32]1[CH2:37][CH2:36][CH2:35][C@H:34]([CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH2:33]1

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of 7-(oxiran-2-yl)-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole (Preparation 13A, 150 mg, 0.353 mmol) and (R)-ethyl 2-(piperidin-3-yl)acetate (90 mg, 0.526 mmol) in 2-propanol (5 mL) was stirred at 85° C. under a nitrogen atmosphere for 5 hr. The reaction mixture was concentrated and purified by silica gel column chromatography using ethyl acetate/heptane followed by 10% methanol in ethyl acetate to afford ethyl 2-((3R)-1-(2-hydroxy-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)ethyl)piperidin-3-yl)acetate (125 mg, 0.210 mmol, 59.4% yield) as a yellow solid. LC/MS M+1=596.3.

Workup

concentrationThe reaction mixture was concentrated
custompurified by silica gel column chromatography

Sources & evidence

ORD record: ord-28aaec595485458bb87fda5311b3ea15
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216972B2

Reaction notes

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