4-Nitrobenzoic Acid → HCID 86681863, compound

HRID 1749370Notes

Reaction equation

HRID 1749370 reaction equation
[OH:1][C@@H:2]1[CH2:7][N:6]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[C@H:5]([CH3:18])[CH2:4][CH2:3]1.CN(C)C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[N+:41]([C:44]1[CH:52]=[CH:51][C:47]([C:48](O)=[O:49])=[CH:46][CH:45]=1)([O-:43])=[O:42].CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[CH3:18][C@@H:5]1[CH2:4][CH2:3][C@@H:2]([O:1][C:48]([C:47]2[CH:46]=[CH:45][C:44]([N+:41]([O-:43])=[O:42])=[CH:52][CH:51]=2)=[O:49])[CH2:7][N:6]1[C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9]

Participants

6

Reactant 4

HCID 61084-Nitrobenzoic AcidHCID 33335924-(Dimethylamino)phenyldiphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 866818641-Piperidinecarboxylic acid, 5-hydroxy-2-methyl-, phenylmethyl ester, (2R,5S)-

Product 1

HCID 86681863HCID 86681863, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a THF (909 ml) solution of benzyl (2R,5S)-5-hydroxy-2-methylpiperidine-1-carboxylate (34 g, 136 mmol), 4-(dimethylamino) phenyldiphenylphosphine (58.3 g, 191 mmol), and 4-nitrobenzoic acid (29.6 g, 177 mmol) was added, under N2, DEAD (30.0 ml, 191 mmol) dropwise at −15 to −25° C. over 20 min. The reaction was allowed to warm to RT overnight. The reaction was concentrated in vacuo, removing most THF, then diluted with Et2O (500 mL). The mixture was cooled at 0° C. and washed with 1 N HCl (5×200 mL). The combined aqueous phases were back-extracted twice with Et2O. The combined organic phases were subsequently washed twice more with 1 N HCl. The organics were dried over MgSO4, filtered, and concentrated. The crude material was purified by silica gel gradient chromatography (0-40% ethyl acetate in hexanes), providing the titled compound as a light yellow oil which slowly solidified. LRMS m/z (M+H) 399.3 found, 399.1 required.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customremoving most THF
  3. additiondiluted with Et2O (500 mL)
  4. temperatureThe mixture was cooled at 0° C.
  5. washwashed with 1 N HCl (5×200 mL)
  6. extractionThe combined aqueous phases were back-extracted twice with Et2O
  7. washThe combined organic phases were subsequently washed twice more with 1 N HCl
  8. dry with materialThe organics were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material was purified by silica gel gradient chromatography (0-40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-b20b2f083f0b4dfcbb66355c481533f7
Source dataset
uspto-grants-2015_10
Patent number
US09156819B2

Reaction notes

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