Benzyl Alcohol → Benzyl 2-(4-(4-(5-aminopyridin-2-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate

HRID 881739Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]34[CH2:21][CH2:20][C:17]([CH2:22][C:23]([O:25][CH3:26])=[O:24])([CH2:18][CH2:19]3)[O:16][CH2:15]4)=[CH:10][CH:9]=2)=[N:6][CH:7]=1.C(O)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[CH:10][C:11]([C:14]34[CH2:19][CH2:18][C:17]([CH2:22][C:23]([O:25][CH2:26][C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)=[O:24])([CH2:20][CH2:21]3)[O:16][CH2:15]4)=[CH:12][CH:13]=2)=[N:6][CH:7]=1

Participants

Conditions

Temperature: 130 °C

Procedure

To a mixture of methyl 2-(4-(4-(5-aminopyridin-2-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate (286 mg, 0.812 mmol) in neat benzyl alcohol (6 mL, 57.9 mmol) was added titanium(IV) isopropoxide (1.5 mL, 5.12 mmol) and 4 A molecular sieves (5 g, 0.812 mmol). The reaction mixture was heated at 130° C. overnight. The reaction was quenched by saturated NaHCO3 and was extracted with EtOAc. The combined organic layer was filtered and washed with brine and dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by prep-HPLC (15 to 90% ACN-water (0.1% NH4OH) with X-bridge C18 column) to give the title compound after drying (150 mg, 43% yield). LC/MS, ESI-MS(+): 429.1, RT: 1.41 (Condition E).

Workup

customThe reaction was quenched by saturated NaHCO3
extractionwas extracted with EtOAc
filtrationThe combined organic layer was filtered
washwashed with brine
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was purified by prep-HPLC (15 to 90% ACN-water (0.1% NH4OH) with X-bridge C18 column)

Sources & evidence

ORD record: ord-1c8cb50d6f2a4ba1a723b64c8b603d5d
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08993619B2

Reaction notes

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