4-Nitrobenzoic Acid → HCID 86657804, compound

HRID 1971964Notes

Reaction equation

HRID 1971964 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([OH:14])[C@H:10]([CH2:15][O:16][C:17]2[N:18]=[N:19][C:20]([CH2:36][CH2:37][CH2:38][CH3:39])=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH:30]4[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]4)=[CH:25][CH:24]=3)[CH:22]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[N+:59]([C:62]1[CH:70]=[CH:69][C:65]([C:66](O)=[O:67])=[CH:64][CH:63]=1)([O-:61])=[O:60].CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.CCOCC>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([O:14][C:66](=[O:67])[C:65]2[CH:64]=[CH:63][C:62]([N+:59]([O-:61])=[O:60])=[CH:70][CH:69]=2)[C@H:10]([CH2:15][O:16][C:17]2[N:18]=[N:19][C:20]([CH2:36][CH2:37][CH2:38][CH3:39])=[C:21]([C:23]3[CH:24]=[CH:25][C:26]([O:29][CH:30]4[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]4)=[CH:27][CH:28]=3)[CH:22]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 61084-Nitrobenzoic AcidHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 86657800HCID 86657800, compound

Product 1

HCID 86657804HCID 86657804, compoundYield 77.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of (±)-cis-3-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxymethyl]-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (Example 43, 1.18 mmol, 0.64 g), PPh3 (1.43 mmol, 0.375 g) and p-nitrobenzoic acid (1.5 mmol, 0.251 g) in anhydrous THF (15 mL) at −60° C. was added DIAD (1.43 mmol. 0.289 mL) over 10 min. The stirring was continued and let the reaction slowly attain room temperature over 3 h. The reaction mixture was diluted with ether (300 mL), washed with water (100 mL) followed by saturated sodium bicarbonate (100 mL). The organic layer was dried, filtered and concentrated under reduced pressure. The residue was purified by flash silica gel flash column chromatography by eluating with 20% ethyl acetate in hexanes to provide (±)-trans-3-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxymethyl]-4-(4-nitro-benzoyloxy)-piperidine-1-carboxylic acid tert-butyl ester (0.63 g).

Workup

  1. customthe reaction slowly attain room temperature over 3 h
  2. washwashed with water (100 mL)
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash silica gel flash column chromatography

Sources & evidence

ORD record
ord-29643b13be924969891ce752caff5d5d
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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