Potassium Phosphate, Tribasic → tert-butyl (3-((3-(3,6-dihydro-2H-pyran-4-yl)pyridin-2-yl)oxy)cyclobutyl)carbamate

HRID 1846766Notes

Reaction equation

Br[C:2]1[C:3]([O:8][CH:9]2[CH2:12][CH:11]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:10]2)=[N:4][CH:5]=[CH:6][CH:7]=1.CC1(C)C(C)(C)CB([C:29]2[CH2:30][CH2:31][O:32][CH2:33][CH:34]=2)C1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[O:32]1[CH2:31][CH:30]=[C:29]([C:2]2[C:3]([O:8][CH:9]3[CH2:12][CH:11]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:10]3)=[N:4][CH:5]=[CH:6][CH:7]=2)[CH2:34][CH2:33]1

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of tert-butyl (3-((3-bromopyridin-2-yl)oxy)cyclobutyl)carbamate (see PREPARATION 7B; 343 mg, 1 mmol), 4-(3,3,4,4-tetramethyl-borolan-1-yl)-3,6-dihydro-2H-pyran (2.27 mg, 1.1 mmol) and K3PO4 (424 mg, 2 mmol) in 1,4-dioxane (60 mL) and H2O (6 mL) was added Pd(dppf)Cl2 (36.6 mg, 0.05 mmol) then the reaction mixture was stirred at 110° C. under N2 for overnight. The reaction mixture was filtered through CELITE® and washed with CH2Cl2. The organic layer was concentrated and the crude product was purified by silica gel column to give tert-butyl (3-((3-(3,6-dihydro-2H-pyran-4-yl)pyridin-2-yl)oxy)cyclobutyl)carbamate (242 mg, 0.7 mmol, yield 70%). ESI-MS (M+1): 347 calc. for C19H26N2O4 346

Workup

filtrationThe reaction mixture was filtered through CELITE®
washwashed with CH2Cl2
concentrationThe organic layer was concentrated
customthe crude product was purified by silica gel column

Sources & evidence

ORD record: ord-33c7c2ee479f446c914d6412bc37e641
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952037B2

Reaction notes

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