Dimethylformamide → HCID 71623306, compound

HRID 1258007Notes

Reaction equation

HRID 1258007 reaction equation
[CH:1]([N:14]1[CH2:17][C:16]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH2:29][C:28]([C:34]4[CH:39]=[C:38]([Cl:40])[C:37]([Cl:41])=[C:36]([Cl:42])[CH:35]=4)([C:30]([F:33])([F:32])[F:31])[O:27][N:26]=3)=[CH:21][C:20]=2Br)([OH:18])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN([CH:47]=[O:48])C>O.[C-]#N.[C-]#N.[Zn+2].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>[CH:1]([N:14]1[CH2:17][C:16]2([C:19]3[C:20](=[CH:21][C:22]([C:25]4[CH2:29][C:28]([C:34]5[CH:39]=[C:38]([Cl:40])[C:37]([Cl:41])=[C:36]([Cl:42])[CH:35]=5)([C:30]([F:33])([F:32])[F:31])[O:27][N:26]=4)=[CH:23][CH:24]=3)[C:47](=[O:48])[O:18]2)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 71623197HCID 71623197, compound

Product 1

HCID 71623306HCID 71623306, compoundYield 58%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 1-benzhydryl-3-(2-bromo-4-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)phenyl)azetidin-3-ol (500 mg, 0.7 mmol) in DMF (12 mL) was added Zn(CN)2 (180 mg, 1.5 mmol) and the reaction was degassed with N2 purge. Pd(PPh3)4 (40 mg, 0.04 mmol) was added and the reaction mixture was heated at 150° C. for 15 minutes under microwave irradiation. The reaction mixture was diluted with water, extracted with EtOAc, dried, and concentrated under vacuum. The crude material was chromatographed (40 g Redi-Sep column) eluting from 100% heptane to 50:50 EtOAc:heptane to afford the intermediate (268 mg, 58%) as a glass. 1HNMR (CDCl3) δ ppm: 8.32 (1H), 8.18 (1H), 7.95 (1H), 7.68 (2H), 7.51 (4H), 7.35-7.23 (6H), 4.55 (1H), 4.15 (1H), 3.79-3.69 (3H), 3.60 (2H); m/z (CI) 657 ([M+H]+.

Workup

  1. customthe reaction was degassed with N2
  2. custompurge
  3. extractionextracted with EtOAc
  4. customdried
  5. concentrationconcentrated under vacuum
  6. customThe crude material was chromatographed (40 g Redi-Sep column)
  7. washeluting from 100% heptane to 50:50 EtOAc

Sources & evidence

ORD record
ord-ee3f857830324434a74077992be2ea52
Source dataset
uspto-grants-2013_06
Patent number
US08466115B2

Reaction notes

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