Tetrahydrofuran → 4-Methyl-5-(1-hydroxy-2-cyclohexylethyl)thiazole

HRID 651045Notes

Reaction equation

[CH3:1][C:2]1[N:3]=[CH:4][S:5][C:6]=1[CH:7]=[O:8].C1COCC1.[CH:14]1([CH2:20][Mg]Br)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1>CCOCC>[CH3:1][C:2]1[N:3]=[CH:4][S:5][C:6]=1[CH:7]([OH:8])[CH2:20][CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1

Participants

Conditions

Temperature: -10 °C

Procedure

A 3-neck, 100 mL round-bottom flask was charged with the product from Example 22D (412.6 mg, 3.5 mmol) and anhydrous THF (15 mL) under N2 atmosphere. The reaction was cooled to −10° C. Cyclohexylmethylmagnesium bromide (7 mL, of a 1.0M solution in ether, 7 mmol) was added dropwise. The reaction was stirred for 1 hour, warmed to room temperature, and stirred for an additional 3 hours. The reaction was quenched with 10 mL THF/1M HCl (1:1). The aqueous and organic layers were separated. The pH ofthe aqueous layer was adjusted to 3 with 1M HCl. The aqueous layer was extracted with EtOAc (3×10 mL). All organic layers were combined and washed with brine, dried (MgSO4), and concentrated under vacuum. The residue was purified by silica gel column (1:1 EtOAc/hexanes) to provide 425.2 mg (58%) of the title compound as an orange oil.

Workup

temperaturewarmed to room temperature
stirringstirred for an additional 3 hours
customThe reaction was quenched with 10 mL THF/1M HCl (1:1)
customThe aqueous and organic layers were separated
extractionThe aqueous layer was extracted with EtOAc (3×10 mL)
washwashed with brine
dry with materialdried (MgSO4)
concentrationconcentrated under vacuum
customThe residue was purified by silica gel column (1:1 EtOAc/hexanes)

Sources & evidence

ORD record: ord-8017d95e887346ae802a57ceded982cd
Source dataset: uspto-grants-2001_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06277871B1

Reaction notes

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