Sodium Methoxide → HCID 57473829, compound

HRID 576594Notes

Reaction equation

HRID 576594 reaction equation
[CH:1]([C:4]([CH2:11][C:12](=[O:36])[NH:13][CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1[O:25][Si:26]([CH:33]([CH3:35])[CH3:34])([CH:30]([CH3:32])[CH3:31])[CH:27]([CH3:29])[CH3:28])([CH2:8][CH:9]=[CH2:10])[C:5]([O-])=[O:6])([CH3:3])[CH3:2].C[O-].[Na+]>CO.CCOC(C)=O>[CH2:8]([C:4]1([CH:1]([CH3:3])[CH3:2])[CH2:11][C:12](=[O:36])[N:13]([CH2:14][C:15]2[CH:20]=[C:19]([C:21]([F:24])([F:22])[F:23])[CH:18]=[CH:17][C:16]=2[O:25][Si:26]([CH:30]([CH3:31])[CH3:32])([CH:27]([CH3:29])[CH3:28])[CH:33]([CH3:34])[CH3:35])[C:5]1=[O:6])[CH:9]=[CH2:10]

Participants

5

Reactant 2

HCID 10942334Sodium MethoxideHCID 57473827HCID 57473827, compound

Product 1

HCID 57473829HCID 57473829, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A 100 mL round bottom flask charged with 2-isopropyl-2-(2-oxo-2-(5-(trifluoromethyl)-2-(trii sopropylsilyloxy)benzylamino)-ethyl)pent-4-enoate (1.40 g, 2.57 mmol) in MeOH (26 mL) was cooled to 0° C. The solution was treated dropwise with sodium methoxide (25% solution in MeOH, 0.048 mL, 0.206 mmol) via syringe over 3 min, and the resulting mixture was stirred for 12 h. At this time mixture was diluted with EtOAc (100 mL) washed with brine (2×20 mL). The organic layer was dried (MgSO4) and concentrated on a rotary evaporator. The residue was purified using a 12 g silica gel cartridge and 20:1 Hex/EtOAc to 3:1 Hex/EtOAc to elute 3-allyl-3-isopropyl-1-(5-(trifluoromethyl)-2-(triisopropylsilyloxy)benzyl)pyrrolidine-2,5-dione (538 mg, 1.05 mmol, 41% yield) as a clear oil. LC/MS [M+H]+=512.12, HPLC tR=2.55 min [Waters Sunfire C18 4.6×50 mm column, 3 min gradient from 10/90/0.1 MeOH/H2O/TFA to 90/10/0.1 MeOH/H2O/TFA at 4 mL/min flow rate]. 1H-NMR (400 MHz, CDCl3) δ=7.38 (d, J=8.0 Hz, 1H), 7.14 (s, 1H), 6.88 (d, J=8.0 Hz, 1H), 5.67 (m, 1H), 5.19 (m, 2H), 4.75 (s, 2H), 2.56 (m, 2H), 2.35 (m, 1H), 2.17 (m, 2H), 1.16 (m, 2H), 0.98 (d, J=6.8 Hz, 3H), 0.92 (d, J=6.8 Hz, 3H).

Workup

  1. washwashed with brine (2×20 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated on a rotary evaporator
  4. customThe residue was purified

Sources & evidence

ORD record
ord-82c84c0f5bfd4dbe83dfeb278821e44f
Source dataset
uspto-grants-2015_05
Patent number
US09040526B2

Reaction notes

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