Water → HCID 66719117, compound

HRID 2362150Notes

Reaction equation

[C:1]([O:5][C:6](=[O:21])[NH:7][C:8]1([C:14]2[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=2)[CH2:11][C:10]([OH:13])([CH3:12])[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].O.[CH3:23][N:24](C=O)C>[Zn].[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].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.[Fe+2]>[C:1]([O:5][C:6](=[O:21])[NH:7][C:8]1([C:14]2[CH:19]=[CH:18][C:17]([C:23]#[N:24])=[CH:16][CH:15]=2)[CH2:11][C:10]([OH:13])([CH3:12])[CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of [1-(4-Bromo-phenyl)-3-hydroxy-3-methyl-cyclobutyl]-carbamic acid tert-butyl ester 2-1 (prepared according to WO2008/070041; 3.56 g, 10 mmol), Zn (1 g, 15 mmol), Zn(CN)2 (1.76 g, 15 mmol), Pd2(dba)3 (0.5 g, 0.5 mmol) and DPPF (300 mg, 0.5 mmol) in 30 mL of DMF was stirred at 100° C. for 2 hrs under N2. After the mixture was cooled to rt, 100 mL of water was added and product was extracted with ethyl acetate 100 mL×3. The organic layer was combined, washed with brine, dried over sodium sulfate and concentrated under vacuum. The residue was purified by silica gel chromatography using EA/PE (1:2) as eluant to give compound 2-2.

Workup

temperatureAfter the mixture was cooled to rt
extractionproduct was extracted with ethyl acetate 100 mL×3
washwashed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated under vacuum
customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record: ord-62ef2f4482964535b7cc137daa6bf74b
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08691825B2

Reaction notes

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