2-Bromothiazole → 8-(1,3-Thiazol-2-yl)-1,4-dioxaspiro[4.5]decan-8-ol

HRID 661363Notes

Reaction equation

HRID 661363 reaction equation
C([Li])CCC.Br[C:7]1[S:8][CH:9]=[CH:10][N:11]=1.[O:12]1[C:16]2([CH2:21][CH2:20][C:19](=[O:22])[CH2:18][CH2:17]2)[O:15][CH2:14][CH2:13]1>C(OCC)C>[S:8]1[CH:9]=[CH:10][N:11]=[C:7]1[C:19]1([OH:22])[CH2:20][CH2:21][C:16]2([O:15][CH2:14][CH2:13][O:12]2)[CH2:17][CH2:18]1

Participants

5

Reactant 3

HCID 764302-BromothiazoleHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 178418339Butyllithium

Product 1

HCID 578033298-(1,3-Thiazol-2-yl)-1,4-dioxaspiro[4.5]decan-8-olYield 94%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a −78° C. solution of n-butyl lithium (10.4 mL, 2.5M in hexane, 26 mmol) in diethyl ether (20 mL) was added 2-bromothiazole (3.28 g, 1.8 mL, 20 mmol) slowly via syringe. The reaction mixture was stirred for 15 minutes, followed by the slow addition of 1,4-dioxaspiro[4.5]decan-8-one (4.22 g, 27 mmol) in diethyl ether (55 mL). The reaction mixture was allowed to warm to ambient temperature and stirred overnight. The reaction mixture was quenched with saturated aqueous ammonium chloride (50 mL) and extracted with two portions of ethyl acetate. The combined organic layers were concentrated. The residue was chromatographed on silica gel eluting with 0%-40% ethyl acetate-hexane to obtain the title compound (4.53 g, 94%). 1H NMR (300 MHz, DMSO-d6) δ ppm 7.69 (d, J=3.2, 1H), 7.55 (d, J=3.2, 1H), 3.88 (s, 4H), 2.11 (td, J=4.2, 12.8, 2H), 1.93-1.80 (m, 2H), 1.80-1.53 (m, 4H).

Workup

  1. stirringstirred overnight
  2. customThe reaction mixture was quenched with saturated aqueous ammonium chloride (50 mL)
  3. extractionextracted with two portions of ethyl acetate
  4. concentrationThe combined organic layers were concentrated
  5. customThe residue was chromatographed on silica gel eluting with 0%-40% ethyl acetate-hexane

Sources & evidence

ORD record
ord-5e416c1ffeea47778f796b883c2a5ce8
Source dataset
uspto-grants-2011_12
Patent number
US08084616B2

Reaction notes

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