Sodium Carbonate → 1-[4-Amino-3-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-cyclohexanecarbonitrile

HRID 2408506Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]#[N:15])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][C:3]=1Br.[CH3:17][C:18]1([CH3:27])[CH2:23][CH2:22][C:21](B(O)O)=[CH:20][CH2:19]1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]#[N:15])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][C:3]=1[C:21]1[CH2:22][CH2:23][C:18]([CH3:27])([CH3:17])[CH2:19][CH:20]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 1-(4-amino-3-bromo-phenyl)-cyclohexane carbonitrile (136 mg, 0.487 mmol, as prepared in the previous step) in DMF (10 mL) was treated with 4,4-dimethyl-cyclohex-1-enylboronic acid (90.0 mg, 0.585 mmol) and Na2CO3 (1.95 mL, 3.90 mmol, 2 M aq). The mixture was degassed via sonication, placed under Ar, treated with Pd(dppf)Cl2 (35.6 mg, 0.0487 mmol), and heated to 80° C. overnight. The cooled mixture was partitioned between EtOAc (50 mL) and water (50 mL). The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers was dried over MgSO4 and concentrated in vacuo. Silica gel chromatography of the residue on a 20-g Isolute SPE column with 10-15% EtOAc-hexane afforded the title compound (45.9 mg, 30%) as a colorless glassy solid. Mass spectrum (ESI, m/z): Calcd. for C21H28N2, 309.2 (M+H), found 309.2.

Workup

customThe mixture was degassed via sonication
customThe cooled mixture was partitioned between EtOAc (50 mL) and water (50 mL)
extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
dry with materialThe combined organic layers was dried over MgSO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-ea923c6529fb4d848a9090ff965baf7f
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815867B2

Reaction notes

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