Lithium diisopropylamide → HCID 58456154, compound

HRID 1039942Notes

Reaction equation

C([N-]C(C)C)(C)C.[Li+].[CH3:9][C:10]1[CH:11]=[C:12]([CH:14]=[C:15]([C:17]2[S:21][CH:20]=[N:19][CH:18]=2)[CH:16]=1)[NH2:13].[CH3:22][C:23]1([CH3:34])[CH:28]([CH3:29])[C:27](=[O:30])[CH2:26][CH2:25][CH:24]1[C:31]([OH:33])=[O:32]>C1COCC1.CCOC(C)=O>[NH2:13][C:12]1[CH:14]=[C:15]([C:17]2[S:21][C:20]([C:27]3([OH:30])[CH2:26][CH2:25][CH:24]([C:31]([OH:33])=[O:32])[C:23]([CH3:22])([CH3:34])[CH:28]3[CH3:29])=[N:19][CH:18]=2)[CH:16]=[C:10]([CH3:9])[CH:11]=1

Participants

Conditions

Temperature: -60 °C

Procedure

Lithium diisopropylamide (5110 μl, 9.20 mmol) was added to a −78° C. solution of 3-methyl-5-(1,3-thiazol-5-yl)aniline (500 mg, 2.63 mmol) in THF (7 mL). The reaction was allowed to warm to −60° C. while aging for 30 min. The solution was cooled to −78° C. and 2,2,3-trimethyl-4-oxocyclohexanecarboxylic acid (600 mg, 3.26 mmol) in THF (6 mL) was added portionwise, maintaining an internal temperature below −65° C. After 5 min at −78° C. the reaction was warmed to room temperature, diluted with EtOAc and washed with aqueous saturated ammonium chloride (3×). The combined aqueous portion was extracted with 10% IPA:CHCl3 (3×). The combined organic layers were dried under reduced pressure to yield 4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-4-hydroxy-2,2,3-trimethylcyclohexanecarboxylic acid (121 mg, 12%) as a yellow oil. MS ESI: [M+H]+ m/z 375.

Workup

temperatureThe solution was cooled to −78° C.
temperaturemaintaining an internal temperature below −65° C
temperatureAfter 5 min at −78° C. the reaction was warmed to room temperature
washwashed with aqueous saturated ammonium chloride (3×)
extractionThe combined aqueous portion was extracted with 10% IPA
customThe combined organic layers were dried under reduced pressure

Sources & evidence

ORD record: ord-deea4f48dc4a4ed0b0af1c6141996ce0
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08551984B2

Reaction notes

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