Triisopropylsilyl chloride → (R)-1-(2-Methoxy-4-nitro-phenyl)-3-triisopropylsilanyloxy-pyrrolidine

HRID 601508Notes

Reaction equation

HRID 601508 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:4]=1[N:12]1[CH2:16][CH2:15][C@@H:14]([OH:17])[CH2:13]1.Cl[Si:19]([CH:26]([CH3:28])[CH3:27])([CH:23]([CH3:25])[CH3:24])[CH:20]([CH3:22])[CH3:21]>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:4]=1[N:12]1[CH2:16][CH2:15][C@@H:14]([O:17][Si:19]([CH:26]([CH3:28])[CH3:27])([CH:23]([CH3:25])[CH3:24])[CH:20]([CH3:22])[CH3:21])[CH2:13]1

Participants

4

Reactant 2

HCID 139400Triisopropylsilyl chlorideHCID 15965522(R)-1-(2-Methoxy-4-nitrophenyl)pyrrolidin-3-ol

Product 1

HCID 57870244(R)-1-(2-Methoxy-4-nitro-phenyl)-3-triisopropylsilanyloxy-pyrrolidineYield 99.4%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve the crude (R)-1-(2-methoxy-4-nitro-phenyl)-pyrrolidin-3-ol (10.9 g, 45.5 mmol) in dry pyridine (50 mL) and chill to 0° C. Add chloro-triisopropyl-silane (19.8 mL, 91 mmol) dropwise and then heat to 80° C. overnight. Remove the pyridine via reduced pressure and then wash the crude material with NaHSO3 solution and extract with EtOAc (3×100 mL). Combine the organic solutions, then dry and concentrate to give the crude product. Purify over a silica plug with hexanes (300 mL) and flush with 10% EtOAc in hexanes (800 mL) to give the title compound as a reddish oil (17.85 g, 99%). MS (ES+) 395.2 (M+1)+. 1H NMR (400 MHz, CDCl3): δ 7.81 (dd, J=8.8, 2.2 Hz, 1H), 7.63 (d, J=2.2 Hz, 1H), 6.45 (d, J=88 Hz, 1H), 4.57-4.52 (m, 1H), 3.84 (s, 3H), 3.84-3.78 (m, 1H), 3.72-3.64 (m, 1H), 3.61-6.53 (m, 1H), 3.45 (dd, J=11.0, 2.2 Hz, 1H), 2.06-1.92 (m, 2H), 1.04-1.01 (m, 21H).

Workup

  1. customRemove the pyridine via reduced pressure
  2. washwash the crude material with NaHSO3 solution
  3. extractionextract with EtOAc (3×100 mL)
  4. customCombine the organic solutions, then dry
  5. concentrationconcentrate
  6. customto give the crude product
  7. customPurify over a silica plug with hexanes (300 mL)
  8. customflush with 10% EtOAc in hexanes (800 mL)

Sources & evidence

ORD record
ord-25d6296f84744bc7903a29f89953f6b8
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

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