Dimethylformamide → HCID 178445788, compound

HRID 713872Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([C:12]([F:15])([F:14])[F:13])=[C:7]([O:16][C@H:17]1[CH2:22][CH2:21][C@H:20]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:19][CH2:18]1)[CH:6]=[CH:5]2.[Li]CCCC.CN([CH:35]=[O:36])C.[NH4+].[Cl-]>C1COCC1>[C:23]([C@H:20]1[CH2:21][CH2:22][C@H:17]([O:16][C:7]2[C:8]([C:12]([F:14])([F:15])[F:13])=[C:9]3[C:4](=[CH:5][CH:6]=2)[CH:3]=[C:2]([CH:35]=[O:36])[CH:11]=[CH:10]3)[CH2:18][CH2:19]1)([CH3:25])([CH3:26])[CH3:24]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 6-bromo-2-(trans-4-tert-butylcyclohexyloxy)-1-(trifluoromethyl)naphthalene (1 g, 2.3 mmol) in THF (30 mL) was added n-BuLi (2.8 mL, 2.5M in THF, 3.0 equiv) dropwise at −78° C. in 30 min, then DMF (840 mg, 11.5 mmol, 5.0 equiv) was added slowly at −78° C. The reaction mixture was stirred at −78° C. for 1.5 h. Then saturated NH4Cl solution was added to the mixture to quench the reaction. The mixture was extracted with EtOAc and purified by silica gel chromatography (petroleum ether:ethyl acetate 10:1) to give product 6-(trans-4-tert-butylcyclohexyloxy)-5-(trifluoromethyl)-2-naphthaldehyde as a yellow solid (608 mg, 70%) ESI-MS: 379.2 (M+H)+. 1H NMR (400 MHz, CDCl3) δ: 10.13 (s, 1H), 8.28 (d, 2H), 8.08 (d, 1H), 7.98-8.01 (dd, 1H), 7.41 (d, 1H), 4.39 (m, 1H), 2.21 (d, 2H), 1.90 (d, 2H), 1.49-1.58 (q, 2H), 1.10-1.17 (m, 3H), 0.86 (s, 9H).

Workup

customto quench
customthe reaction
extractionThe mixture was extracted with EtOAc
custompurified by silica gel chromatography (petroleum ether:ethyl acetate 10:1)

Sources & evidence

ORD record: ord-6404a06bebd0474facacbd0815ee54c5
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09186367B2

Reaction notes

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