2-Bromobenzyl alcohol → 8-[2-(Hydroxymethyl)phenyl]-1,4-dioxaspiro[4.5]decan-8-ol

HRID 1025682Notes

Reaction equation

Br[C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][OH:5].[Li]CCCC.[CH2:15]1[O:25][C:18]2([CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]2)[O:17][CH2:16]1>C1COCC1>[OH:5][CH2:4][C:3]1[CH:6]=[CH:7][CH:8]=[CH:9][C:2]=1[C:21]1([OH:24])[CH2:22][CH2:23][C:18]2([O:25][CH2:15][CH2:16][O:17]2)[CH2:19][CH2:20]1

Participants

Conditions

Temperature: -4 °C

Procedure

To a solution of 2-bromobenzyl alcohol (3.0 g, 16 mmol) in THF (40 mL) cooled at −78° C. was added a 2.5 M solution of n-BuLi in hexanes (14.1 mL). The mixture was stirred at −4° C. for 1 hour and cooled back to −78° C. To it was added a solution of 1,4-cyclohexanedione mono-ethylene ketal (2.5 g, 16 mmol) in TIE (10 mL) over 15 minutes. Stirring was continued at −78° C. for 30 minutes and at −4° C. for 1 hour. The reaction was quenched by addition of a solution of NH4Cl in water. The resulting solution was extracted with EtOAc three times. The combined extract was washed with brine, dried over MgSO4 and concentrated. Purification on silica gel eluting with 5% MeOH/CH2Cl2 provided the title compound. MS calculated (M+H)+ 265, found 287 (M+Na)+.

Workup

temperaturecooled back to −78° C
stirringStirring
waitwas continued at −78° C. for 30 minutes and at −4° C. for 1 hour
customThe reaction was quenched by addition of a solution of NH4Cl in water
extractionThe resulting solution was extracted with EtOAc three times
extractionThe combined extract
washwas washed with brine
dry with materialdried over MgSO4
concentrationconcentrated
customPurification on silica gel eluting with 5% MeOH/CH2Cl2

Sources & evidence

ORD record: ord-a285c5cecc5441239cfa2db866ebbf76
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08729063B2

Reaction notes

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