Thiazole → Ethyl 4-[hydroxy(1,3-thiazol-2-yl)methyl]cyclohexanecarboxylate

HRID 928101Notes

Reaction equation

C([Mg]Cl)(C)C.[Li+].[Cl-].[S:8]1[CH:12]=[CH:11][N:10]=[CH:9]1.[CH:13]([CH:15]1[CH2:20][CH2:19][CH:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:17][CH2:16]1)=[O:14]>C1COCC1>[OH:14][CH:13]([C:9]1[S:8][CH:12]=[CH:11][N:10]=1)[CH:15]1[CH2:16][CH2:17][CH:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:19][CH2:20]1

Participants

Conditions

Temperature: 5 °C

Procedure

To a 500 mL round bottom flask was added iPrMgCl-LiCl (1.3 M in THF, 99 mL, 129 mmol) and the solution cooled in an ice bath. Thiazole (9.7 mL, 135 mmol) was then introduced at such a rate that the internal temperature did not exceed 5° C. and then the thick slurry was stirred for 1 h. 100 mL of THF was introduced and the reaction mixture cooled to −50° C. at which point ethyl 4-formylcyclohexanecarboxylate (23 g) was added as a solution in THF (100 mL) via cannula. When complete the reaction mixture was permitted to warm slowly to 5° C. where it was stirred for 30 min then quenched by the addition of water and EtOAc. The layers were separated, the organic mixture dried with MgSO4, filtered and concentrated in vacuo to afford ethyl 4-[hydroxy(1,3-thiazol-2-yl)methyl]cyclohexanecarboxylate as a 3:2 mixture of trans:cis isomers both of which are racemic mixtures. This brown oil was used directly in the subsequent step without further manipulation.

Workup

temperaturethe solution cooled in an ice bath
customdid not exceed 5° C.
stirringwas stirred for 30 min
customthen quenched by the addition of water and EtOAc
customThe layers were separated
dry with materialthe organic mixture dried with MgSO4
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-9e494b057b444c0cb316ca3bbc0de01f
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290490B2

Reaction notes

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