3-Butenenitrile → HCID 90177867, compound

HRID 1499301Notes

Reaction equation

HRID 1499301 reaction equation
[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([S:19][CH3:20])[O:7][C@H:6]1[C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[C:23]([CH2:28][C:29]2[CH:34]=[CH:33][C:32](Cl)=[CH:31][CH:30]=2)[CH:22]=1)(=[O:3])[CH3:2].[C:36](#[N:40])[CH2:37][CH:38]=[CH2:39].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.C1(C(N)C2CCCCC2)CCCCC1>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].CN1CCCC1=O>[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([S:19][CH3:20])[O:7][C@H:6]1[C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[C:23]([CH2:28][C:29]2[CH:34]=[CH:33][C:32](/[CH:39]=[CH:38]/[CH2:37][C:36]#[N:40])=[CH:31][CH:30]=2)[CH:22]=1)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 80093-ButenenitrileHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 10774245alpha-CyclohexylcyclohexanemethanamineHCID 90176969HCID 90176969, compound

Product 1

HCID 90177867HCID 90177867, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
160 °C

Procedure

A 5 mL microwave vial was charged with (2S,3S,4R,5S,6R)-2-(3-(4-chlorobenzyl)-4-methylphenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triyl triacetate (7, 208 mg, 0.40 mmol), but-3-enenitrile (0.10 mL, 1.2 mmol), Pd2 dba3 (37 mg, 0.040 mmol), tri(tert-butyl)phosphonium tetrafluoroborate (46 mg, 0.16 mmol), dicyclohexylmethylamine (0.25 mL, 1.2 mmol), and 2 mL of N-methylpyrrolidinone. The reaction was heated in the microwave at 160° C. for 20 min. The reaction was filtered over Celite with excess EtOAc. The organic layer was washed with H2O, saturated aqueous NaHSO4, and brine. It was dried with MgSO4 and concentrated in vacuo. Flash chromatography (gradient 10-80% EtOAc/hexanes) provided the Heck adduct 28 (140 mg, 64% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.24-7.31 (m, 2 H), 7.11-7.20 (m, 2H), 7.02-7.09 (m, 3 H), 6.70 (dt, J=15.9, 1.6 Hz, 1 H), 6.01 (dt, J=15.8, 5.7 Hz, 1 H), 5.33 (t, J=9.3 Hz, 1 H), 5.21 (t, J=9.7 Hz, 1 H), 5.12 (t, J=9.6 Hz, 1 H), 4.52 (d, J=9.9 Hz, 1 H), 4.39 (d, J=9.9 Hz, 1 H), 3.95 (d, J=3.5 Hz, 2 H), 3.28 (dd, J=5.8, 1.8 Hz, 2 H), 2.20 (s, 3 H), 2.16 (s, 3 H), 2.09 (s, 3 H), 2.01 (s, 3 H), 1.75 (s, 3 H). MS (ES+) [M+NH4]+=567.

Workup

  1. filtrationThe reaction was filtered over Celite with excess EtOAc
  2. washThe organic layer was washed with H2O, saturated aqueous NaHSO4, and brine
  3. dry with materialIt was dried with MgSO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-62089132eadd42979998979101d600e7
Source dataset
uspto-grants-2015_12
Patent number
US09200025B2

Reaction notes

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