Triisopropyl borate → tert-Butyl [5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)pyridin-2-yl]methylcarbamate

HRID 1698098Notes

Reaction equation

[Li]C[CH2:3][CH2:4][CH3:5].Br[C:7]1[CH:8]=[CH:9][C:10]([CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[N:11][CH:12]=1.[CH:22]([O:25][B:26](OC(C)C)[O:27][CH:28](C)C)(C)C.OCC(C)(CO)C>C1COCC1>[C:17]([O:16][C:15](=[O:21])[NH:14][CH2:13][C:10]1[CH:9]=[CH:8][C:7]([B:26]2[O:27][CH2:28][C:4]([CH3:3])([CH3:5])[CH2:22][O:25]2)=[CH:12][N:11]=1)([CH3:20])([CH3:19])[CH3:18]

Participants

Conditions

Temperature: -78 °C

Procedure

n-BuLi (27 mL, 2.5 M) was slowly added to a stirred solution of tert-butyl (5-bromopyridin-2-yl)methylcarbamate (17.7 g, 61.6 mmol) in THF (280 mL) at −78° C. under an argon atmosphere. After 5 min at −78° C., triisopropylborate (28.5 mL, 123 mmol) was added and the mixture was stirred at −78° C. for 1 h. Neopentyl glycol (6.4 g, 61.4 mmol) was added and the reaction mixture was allowed to reach rt and was stirred for 2.5 d. The reaction was quenched with water (300 mL). The phases were separated and the aqueous phase was extracted with DCM. The organic layer was concentrated and the residue was purified by two successive flash chromatographies (Heptane/EtOAc 9:1→1:4 and DCM/MeOH 24:1 respectively) to give the product (2.23 g) as a white solid. 1H NMR δ 8.57 (dd, 1H) 7.94 (dd, 1H) 7.65 (dd, 1H) 3.76 (s, 4H) 3.30 (s, 3H) 1.47 (s, 9H) 0.96 (s, 6H).

Workup

customto reach rt
stirringwas stirred for 2.5 d
customThe reaction was quenched with water (300 mL)
customThe phases were separated
extractionthe aqueous phase was extracted with DCM
concentrationThe organic layer was concentrated
customthe residue was purified by two successive flash chromatographies (Heptane/EtOAc 9:1→1:4 and DCM/MeOH 24:1 respectively)

Sources & evidence

ORD record: ord-d26c8a4f37e7411e99d8d605af81f8c3
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08163928B2

Reaction notes

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