Dichloromethane → HCID 59432300, compound

HRID 507159Notes

Reaction equation

HRID 507159 reaction equation
[F-].[Cs+].[F:3][C:4]([F:41])([F:40])[C:5]1[CH:6]=[C:7]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[CH2:8][N:9]([C@H:16]1[CH2:22][CH2:21][CH2:20][NH:19][C:18]2[C:23](Br)=[C:24]([C:28]([F:31])([F:30])[F:29])[C:25]([CH3:27])=[CH:26][C:17]1=2)[C:10]1[N:11]=[N:12][N:13]([CH3:15])[N:14]=1.[CH3:42]B(O)O.ClCCl>O1CCOCC1>[F:3][C:4]([F:41])([F:40])[C:5]1[CH:6]=[C:7]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[CH2:8][N:9]([C@H:16]1[CH2:22][CH2:21][CH2:20][NH:19][C:18]2[C:23]([CH3:42])=[C:24]([C:28]([F:31])([F:30])[F:29])[C:25]([CH3:27])=[CH:26][C:17]1=2)[C:10]1[N:11]=[N:12][N:13]([CH3:15])[N:14]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 25953Cesium fluorideHCID 139377Methylboronic AcidHCID 59432473HCID 59432473, compound

Product 1

HCID 59432300HCID 59432300, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Add cesium fluoride (2.44 g, 16.1 mmol) to a mixture of (S)-(3,5-Bis-trifluoromethyl-benzyl)-(9-bromo-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine and methyl boronic acid (0.820 g, 13.8 mmol) in dioxane (50.0 mL). Purge the mixture with nitrogen for 15 min. Add 1,1′-bis(diphenylphosphino)ferrocene palladium (II) chloride, complex with dichloromethane (0.290 g, 0.355 mmol) under nitrogen. Heat the reaction mixture for 3 h. Cool down to room temperature and then evaporate the solvent under reduced pressure. Partition the residue between ethyl acetate (100 mL) and water (100 mL). Separate the layers and extract the aqueous with more ethyl acetate (2×50 mL). Combine the organic layers, dry over Na2SO4, filter and concentrate. Purify the residue by column chromatography on silica gel, eluting with ethyl acetate/hexanes (0-35%), to provide the title compound as an off-white solid (2.16 g, 83%). MS (ES+): 567 (M+H).

Workup

  1. customPurge the mixture with nitrogen for 15 min
  2. temperatureHeat the reaction mixture for 3 h
  3. customevaporate the solvent under reduced pressure
  4. customPartition the residue between ethyl acetate (100 mL) and water (100 mL)
  5. customSeparate the layers
  6. extractionextract the aqueous with more ethyl acetate (2×50 mL)
  7. dry with materialCombine the organic layers, dry over Na2SO4
  8. filtrationfilter
  9. concentrationconcentrate
  10. customPurify the residue by column chromatography on silica gel
  11. washeluting with ethyl acetate/hexanes (0-35%)

Sources & evidence

ORD record
ord-6292e113d107432c983ab65c49b66e3d
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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