HCID 68294906, compound → HCID 68295247, compound

HRID 572498Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH2:13][C:14]2[CH:23]=[CH:22][CH:21]=[CH:20][C:15]=2[C:16]([NH:18][CH3:19])=[O:17])[C:5]([CH3:12])=[C:6]2[C:11]=1[O:10][CH2:9][CH2:8][CH2:7]2.[Li]CCCC.[CH3:29][O:30][C:31]1([CH3:42])[C:36]([O:38][CH3:39])([CH3:37])[O:35][C@@H:34](C#N)[CH2:33][O:32]1>C1COCC1>[CH3:39][O:38][C:36]1([CH3:37])[C:31]([O:30][CH3:29])([CH3:42])[O:32][C@@H:33]([C:19]2[NH:18][C:16](=[O:17])[C:15]3[C:14]([C:13]=2[C:4]2[C:5]([CH3:12])=[C:6]4[C:11](=[C:2]([F:1])[CH:3]=2)[O:10][CH2:9][CH2:8][CH2:7]4)=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:34][O:35]1

Participants

Conditions

Temperature: 0 °C

Procedure

An ice cooled suspension of 2-((8-fluoro-5-methylchroman-6-yl)methyl)-N-methylbenzamide (300 mg, 0.957 mmol) in THF (5 mL) was treated with 2.5M nBuLi in hexanes (804 μl, 2.010 mmol). Upon addition of the n-BuLi, the reaction became homogeneous and dark red in color. After 10 min, a solution of (2S)-5,6-dimethoxy-5,6-dimethyl-1,4-dioxane-2-carbonitrile (289 mg, 1.436 mmol) in THF (0.5 mL) was added and the colorless solution was maintained at 0° C. for 5 min. The reaction was quenched with sat. aq. NH4Cl and extracted with EtOAc. The combined organics were washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified by ISCO (0-10% MeOH-DCM) to afford the title compound (408 mg, 0.844 mmol, 88% yield) as a 1:1 mixture of diastereomers as a pale yellow foam. LC/MS (m/z) ES+=484 (M+1). Rt=2.17, 2.20.

Workup

customThe reaction was quenched with sat. aq. NH4Cl
extractionextracted with EtOAc
washThe combined organics were washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe residue was purified by ISCO (0-10% MeOH-DCM)

Sources & evidence

ORD record: ord-6f39df1367a8400f83013f084c94183e
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09029391B2

Reaction notes

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