Methyl iodide → (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(5'-chloro-2'-vinylbiphenyl-4-yl)-4-methoxypyrrolidine-1,2-dicarboxylate

HRID 1043427Notes

Reaction equation

HRID 1043427 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([CH:35]=[CH2:36])=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C@@:16]3([OH:34])[CH2:20][N:19]([C:21]([O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])=[O:22])[C@H:18]([C:30]([O:32][CH3:33])=[O:31])[CH2:17]3)=[CH:12][CH:11]=2)[CH:9]=1.[CH3:37]I>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([CH:35]=[CH2:36])=[C:8]([C:10]2[CH:11]=[CH:12][C:13]([C@@:16]3([O:34][CH3:37])[CH2:20][N:19]([C:21]([O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:27])[CH3:28])=[O:22])[C@H:18]([C:30]([O:32][CH3:33])=[O:31])[CH2:17]3)=[CH:14][CH:15]=2)[CH:9]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59266523(2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(5'-chloro-2'-vinylbiphenyl-4-yl)-4-hydroxypyrrolidine-1,2-dicarboxylate

Product 1

HCID 59266494(2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(5'-chloro-2'-vinylbiphenyl-4-yl)-4-methoxypyrrolidine-1,2-dicarboxylateYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NaH (60% in oil) (106 mg, 2.65 mmol) was added to a solution of (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(5′-chloro-2′-vinylbiphenyl-4-yl)-4-hydroxypyrrolidine-1,2-dicarboxylate (740 mg, 1.474 mmol) and methyl iodide (0.166 mL, 2.65 mmol) at 0° C. in DMF and stirred at this temperature and allowed to warm up to r.t. overnight. The reaction was then quenched with saturated NH4Cl solution and ether. The ether layer was washed with brine, dried, filtered and evaporated to give crude material. The crude material was purified by flash chromatography on the Biotage (5-40% EtOAc in hexanes) to give semi purified product (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-(5′-chloro-2′-vinylbiphenyl-4-yl)-4-methoxypyrrolidine-1,2-dicarboxylate (333 mg, 0.645 mmol, 44% yield) as a clear oil. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 0.04 (s, 9H) 1.01-1.06 (m, 2H) 2.52 (dd, J=13.12, 8.85 Hz, 1H) 2.78-2.87 (m, 1H) 2.97 (d, J=5.19 Hz, 3H) 3.65 (s, 1H) 3.67-3.75 (m, 3H) 3.77 (d, J=8.85 Hz, 3H) 3.96-4.08 (m, 1H) 5.21 (d, J=10.99 Hz, 1H) 5.68 (d, J=17.40 Hz, 1H) 6.59 (ddd, J=17.47, 11.06, 2.29 Hz, 1H) 7.26 (d, J=2.14 Hz, 1H) 7.29-7.35 (m, 3H) 7.35-7.40 (m, 2H) 7.56 (d, J=8.24 Hz, 1H).

Workup

  1. customThe reaction was then quenched with saturated NH4Cl solution and ether
  2. washThe ether layer was washed with brine
  3. customdried
  4. filtrationfiltered
  5. customevaporated
  6. customto give crude material
  7. customThe crude material was purified by flash chromatography on the Biotage (5-40% EtOAc in hexanes)
  8. customto give semi

Sources & evidence

ORD record
ord-a5f8e043ae0c48d49e29e15adfae6059
Source dataset
uspto-grants-2013_10
Patent number
US08563505B2

Reaction notes

Loading…