Ethyl (3S)-piperidine-3-carboxylate → (3S)-ethyl 1-(2-(3-(3,4-diethoxyphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)-2-hydroxyethyl)piperidine-3-carboxylate

HRID 1506478Notes

Reaction equation

HRID 1506478 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:13]2[O:17][N:16]=[C:15]3[C:18]4[C:23]([CH2:24][CH2:25][C:14]=23)=[CH:22][C:21]([CH:26]2[CH2:28][O:27]2)=[CH:20][CH:19]=4)[CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH3:12])[CH3:2].[NH:29]1[CH2:34][CH2:33][CH2:32][C@H:31]([C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:30]1>CC(O)C.O1CCOCC1.CN(C1C=CN=CC=1)C>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:13]2[O:17][N:16]=[C:15]3[C:18]4[C:23]([CH2:24][CH2:25][C:14]=23)=[CH:22][C:21]([CH:26]([OH:27])[CH2:28][N:29]2[CH2:34][CH2:33][CH2:32][C@H:31]([C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:30]2)=[CH:20][CH:19]=4)[CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH3:12])[CH3:2]

Participants

6

Reactant 2

HCID 187784Ethyl (3S)-piperidine-3-carboxylateHCID 866699223-(3,4-Diethoxyphenyl)-7-(oxiran-2-yl)-4,5-dihydronaphtho[1,2-c]isoxazole

Product 1

HCID 86669923(3S)-ethyl 1-(2-(3-(3,4-diethoxyphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)-2-hydroxyethyl)piperidine-3-carboxylateYield 26.5%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 3776IsopropanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

To 3-(3,4-diethoxyphenyl)-7-(oxiran-2-yl)-4,5-dihydronaphtho[1,2-c]isoxazole (Preparation 81A, 0.08 g, 0.212 mmol) in a mixture of 2-propanol (1 mL) and dioxane (1.000 mL) was added DMAP (5.18 mg, 0.042 mmol) followed by (S)-ethyl piperidine-3-carboxylate (0.033 mL, 0.212 mmol) at room temperature. The reaction mixture was heated at 60° C. (oil bath temp.) for 26 h, concentrated under reduced pressure, and purified by column chromatography using an ISCO setup (12 g, RediSep® silica gel column). The desired fractions were collected and concentrated to yield (0.03 g, 0.056 mmol, 26.5% yield) of the product as a diastereomeric mixture. The individual diastereomers were separated using a CHIRALCE1® OJ-H column under SFC conditions (25% MeOH with 0.1% diethylamine in CO2). Isomer 1 (7.7 mgs), retention time on chiral HPLC, 4.39 min; Isomer 2 (9 mgs), retention time on chiral HPLC, 6.15 min. The absolute stereochemistry at the carbon anchoring the secondary alcohol, of Isomer 1 and Isomer 2 was not determined.

Workup

  1. concentrationconcentrated under reduced pressure
  2. custompurified by column chromatography
  3. customThe desired fractions were collected
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-f494c845078a4125a1264bc2b567a4a9
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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