Potassium Carbonate → (5R,6S)-6-biphenyl-4-yl-3-(3,5-dichlorophenyl)-1-methyl-1,3-diazaspiro[4.4]nonane-2,4-dione

HRID 1792871Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:27][CH2:26][CH2:25][C@:9]32[N:13]([CH3:14])[C:12](=[O:15])[N:11]([C:16]2[CH:21]=[C:20]([Cl:22])[CH:19]=[C:18]([Cl:23])[CH:17]=2)[C:10]3=[O:24])=[CH:4][CH:3]=1.[C:28]1(B(O)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C([O-])([O-])=O.[K+].[K+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:2]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:27][CH2:26][CH2:25][C@:9]32[N:13]([CH3:14])[C:12](=[O:15])[N:11]([C:16]2[CH:21]=[C:20]([Cl:22])[CH:19]=[C:18]([Cl:23])[CH:17]=2)[C:10]3=[O:24])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of (5R*,6S*)-6-(4-bromophenyl)-3-(3,5-dichlorophenyl)-1-methyl-1,3-diazaspiro[4.4]nonane-2,4-dione (80 mg, 0.17 mmol) (Example 1), phenylboronic acid (73 mg, 0.6 mmol), (Ph3P)4Pd (20 mg, 0.02 mmol) and K2CO3 (80 mg, 0.6 mmol) in a mixture of DME (1.5 ml) and water (50 μl) was heated at 80° C. for 12 h. The insoluble material was filtered off and the filtrate concentrated. After chromatography, (5R*,6S*)-6-biphenyl-4-yl-3-(3,5-dichlorophenyl)-1-methyl-1,3-diazaspiro[4.4]nonane-2,4-dione (20 mg) was obtained as a white solid. 1H NMR (CDCl3): 7.5–7.6 (4H, m), 7.3–7.5 (3H, m), 7.15–7.3 (3H, m), 6.64 (2H, m), 3.45 (1H, dd, J1=12.4 Hz, J2=6.1 Hz), 3.18 (3H, s), 2.5–2.75 (1H, m), 1.8–2.45 (5H, m).

Workup

filtrationThe insoluble material was filtered off
concentrationthe filtrate concentrated

Sources & evidence

ORD record: ord-c46e7e76268b42ab83507814dbe2a19a
Source dataset: uspto-grants-2006_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07078420B2

Reaction notes

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