Methyl Acrylate → HCID 59458963, compound

HRID 238859Notes

Reaction equation

HRID 238859 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@@:9]([NH:31][S@@:32]([C:34]([CH3:37])([CH3:36])[CH3:35])=[O:33])([C:17]2[CH:22]=[C:21]([O:23][C:24]([F:29])([F:28])[CH:25]([F:27])[F:26])[CH:20]=[C:19]([F:30])[CH:18]=2)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:5]=[CH:6][C:7]=1[F:8].[C:38]([O:42][CH3:43])(=[O:41])[CH:39]=[CH2:40].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.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]>[CH3:36][C:34]([CH3:37])([S@:32]([NH:31][C@:9]([C:4]1[CH:3]=[CH:2][C:7]([F:8])=[C:6](/[CH:40]=[CH:39]/[C:38]([O:42][CH3:43])=[O:41])[CH:5]=1)([C:17]1[CH:22]=[C:21]([O:23][C:24]([F:29])([F:28])[CH:25]([F:27])[F:26])[CH:20]=[C:19]([F:30])[CH:18]=1)[CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:33])[CH3:35]

Participants

7

Reactant 4

HCID 7294Methyl AcrylateHCID 10796Cesium carbonateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 59458986HCID 59458986, compound

Product 1

HCID 59458963HCID 59458963, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (R)—N—((S)-1-(3-bromo-4-fluorophenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)-phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide, prepared as described in Procedure 3, 62, 5 and 6, (500 mg, 0.82 mmol) in DMF (5 mL) at rt was added methyl acrylate (0.74 mL, 8.22 mmol), Pd2 (dba)3 (75 mg, 0.082 mmol), tri-t-butyl phosphine (89 μL, 0.33 mmol), and cesium carbonate (536 mg, 1.64 mmol). The reaction mixture was degassed with argon and was heated at 100° C. for 4 h. The reaction mixture was poured into water and the aqueous phase extracted with ethyl acetate. The combined organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by ISCO chromatography (4 g column, 0-40% EtOAc/hexane) to yield (E)-methyl 3-(5-((R)-1-((R)-1,1-dimethylethylsulfinamido)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-fluorophenyl)acrylate as a white foam (485 mg, 96% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.77 (d, J=16.42 Hz, 1H), 7.59 (dd, J=6.69, 2.15 Hz, 1H), 7.41 (m, 1H), 7.16 (m, 4H), 6.94 (dd, J=7.33, 1.77 Hz, 2H), 6.86 (d, J=8.84 Hz, 1H), 6.73 (t, J=4.93 Hz, 2H), 6.53 (d, J=16.17 Hz, 1H), 5.88 (m, 1H), 4.29 (s, 1H), 4.03 (d, J=12.38 Hz, 1H), 3.79 (s, 3H), 3.62 (d, J=12.38 Hz, 1H), 1.24 (m, 9H).

Workup

  1. customThe reaction mixture was degassed with argon
  2. additionThe reaction mixture was poured into water
  3. extractionthe aqueous phase extracted with ethyl acetate
  4. dry with materialThe combined organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by ISCO chromatography (4 g column, 0-40% EtOAc/hexane)

Sources & evidence

ORD record
ord-b28a874dbca74dcfa63a7d1f4509d351
Source dataset
uspto-grants-2014_02
Patent number
US08642576B2

Reaction notes

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