Dichloromethane → HCID 57528927, compound

HRID 1454046Notes

Reaction equation

HRID 1454046 reaction equation
[CH:1]([Sn](CCCC)(CCCC)CCCC)=[CH2:2].Br[C:17]1[CH:18]=[C:19]([C:23]2[O:24][C:25]([CH3:46])=[C:26]([CH2:28][CH2:29][O:30][C:31]3[CH:32]=[C:33]4[C:37](=[CH:38][CH:39]=3)[C@H:36]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:35][CH2:34]4)[N:27]=2)[CH:20]=[CH:21][CH:22]=1.ClCCl>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.Cl[Pd]Cl.[Fe+2].C1(C)C=CC=CC=1>[CH3:46][C:25]1[O:24][C:23]([C:19]2[CH:20]=[CH:21][CH:22]=[C:17]([CH:1]=[CH2:2])[CH:18]=2)=[N:27][C:26]=1[CH2:28][CH2:29][O:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[C@H:36]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:35][CH2:34]2

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 81998TributylvinyltinHCID 86598051HCID 86598051, compound

Product 1

HCID 57528927HCID 57528927, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of vinyltributyltin (Aldrich, 65.0 mg, 0.21 mmol), ethyl ((1S)-5-{2-[2-(3-bromophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy}-2,3-dihydro-1H-inden-1-yl)acetate (50 mg, 0.10 mmol), and [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (4.2 mg, 0.005 mmol) was added toluene (2 mL). The resulting solution was degassed with argon for 30 minutes, and then stirred at 110° C. for 16 h. The reaction mixture was cooled to rt and diluted with 10 mL ethyl acetate. The organic layer was filtered through a silica plug and the filtrate concentrated under reduced pressure. The crude was then redissolved in methanol and filtered through a silica-octyl plug before preparative HPLC purification using 30 to 100% acetonitrile in water (0.1% TFA) gradient to afford the desired product. 1H NMR (CD2Cl2) δ 8.03 (s, 1H), 7.86 (d, 1H), 7.39-7.51 (m, 2H), 7.04 (d, 1H), 6.68-6.84 (m, 3H), 5.88 ( (d, 1H), 5.31-5.35 (m, 1H), 4.10-4.23 (m, 4H), 3.48 (qr, 1H), 2.97 (t, 2H), 2.64-2.89 (m, 3H), 2.29-2.42 (m, 5H), 1.69-1.76 (m, 1H), 1.26 (t, 3H).

Workup

  1. customThe resulting solution was degassed with argon for 30 minutes
  2. temperatureThe reaction mixture was cooled to rt
  3. additiondiluted with 10 mL ethyl acetate
  4. filtrationThe organic layer was filtered through a silica plug
  5. concentrationthe filtrate concentrated under reduced pressure
  6. dissolutionThe crude was then redissolved in methanol
  7. filtrationfiltered through a silica-octyl plug before preparative HPLC purification

Sources & evidence

ORD record
ord-113c8bed9f22479fbd77b8a18f8afe09
Source dataset
uspto-grants-2009_01
Patent number
US07476742B2

Reaction notes

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