2-Bromopyrimidine → 8-(2-Pyrimidinyl)-1,4-dioxaspiro[4.5]decan-8-ol

HRID 2103366Notes

Reaction equation

Br[C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])CCC.[O:13]1[C:17]2([CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]2)[O:16][CH2:15][CH2:14]1>C(Cl)Cl.CCCCCC>[N:3]1[CH:4]=[CH:5][CH:6]=[N:7][C:2]=1[C:20]1([OH:23])[CH2:21][CH2:22][C:17]2([O:16][CH2:15][CH2:14][O:13]2)[CH2:18][CH2:19]1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 2-bromopyrimidine (0.20 g, 1.258 mmol) in dry methylene chloride (3.0 mL) was dropwise added 1.6 M of n-butyllithium in hexane (0.86 mL) at −78° C. The reaction mixture was stirred for 29 min at −78° C. and 1,4-dioxa-spiro[4.5]decan-8-one (0.196 g, 1.26 mmol) in CH2Cl2 (3 mL) was added dropwise. The reaction was stirred at −78° C. for 50 min and quenched with an aqueous solution of NH4Cl. After being warmed to room temperature, the mixture was extracted with CH2Cl2 three times. The combined extracts were dried over MgSO4, filtered and concentrated in vacuo to provide 0.50 g of crude product. Purification by column chromatography on silica gel eluting with 0→50% EtOAc in hexanes provided 0.159 g (54%) of desired product as a light brown-yellow solid. MS (M+H)+ 237.2.

Workup

customat −78° C
stirringThe reaction was stirred at −78° C. for 50 min
customquenched with an aqueous solution of NH4Cl
temperatureAfter being warmed to room temperature
extractionthe mixture was extracted with CH2Cl2 three times
dry with materialThe combined extracts were dried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customto provide 0.50 g of crude product
customPurification by column chromatography on silica gel eluting with 0→50% EtOAc in hexanes

Sources & evidence

ORD record: ord-4b0a0661269d4ee4aca8e03ee869d199
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07576089B2

Reaction notes

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