HCID 11234748, compound → HCID 11394346, compound

HRID 494871Notes

Reaction equation

HRID 494871 reaction equation
CON(C)[C:4](=[O:28])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]2[CH:12]=[CH:13][C:14]3[O:18][C:17]([CH2:19][CH2:20][N:21]4[CH2:25][CH2:24][CH2:23][C@H:22]4[CH3:26])=[CH:16][C:15]=3[CH:27]=2)[CH:6]=1.[CH2:30]([Mg]Br)[CH3:31]>O1CCCC1>[CH3:26][C@@H:22]1[CH2:23][CH2:24][CH2:25][N:21]1[CH2:20][CH2:19][C:17]1[O:18][C:14]2[CH:15]=[CH:27][C:11]([C:7]3[CH:6]=[C:5]([C:4](=[O:28])[CH2:30][CH3:31])[CH:10]=[CH:9][CH:8]=3)=[CH:12][C:13]=2[CH:16]=1

Participants

4

Reactant 2

HCID 11234748HCID 11234748, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 11394346HCID 11394346, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

The product from Example 145 (20 mg, 0.05 mmol) was dissolved into tetrahydrofuran (900 μL), cooled to 0° C., and treated with 1.0 M ethylmagnesium bromide in tetrahydrofuran (150 μL, 150 μmol). The reaction mixture was then stirred at room temperature overnight, quenched by the addition of saturated aqueous NH4Cl, and diluted with EtOAc. The aqueous phase was separated and extracted with EtOAc, and the combined organic phases were washed consecutively with 0.5 M aqueous dipotassium hydrogen phosphate and brine, concentrated, and purified by HPLC [Waters Nova-Pak HR C18 column (25 mm×100 mm, 6 μm particle size) using a gradient of 10% to 100% MeCN/0.1% aqueous TFA over 8 min (10 min run time) at a flow rate of 40 mL/min.] to provide the title compound (44% yield). MS (ESI APCI) m/z 362 (M+H)+; 1HNMR (300 MHz, CD3OD) δ 1.18 (d, 3H), 1.21 (t, 3H), 1.39-1.53 (m, 1H), 1.74-1.87 (m, 2H), 1.95-2.09 (m, 1H), 2.24-2.37 (m, 1H), 2.42-2.61 (m, 2H), 2.94-3.18 (m, 4H), 3.20-3.35 (m, 2H), 6.63 (s, 1H), 7.50-7.52 (m, 2H), 7.58 (dd, 1H), 7.77-7.79 (m, 1H), 7.87 (ddd, 1H), 7.96 (ddd, 1H), 8.22 (dd, 1H).

Workup

  1. customquenched by the addition of saturated aqueous NH4Cl
  2. additiondiluted with EtOAc
  3. customThe aqueous phase was separated
  4. extractionextracted with EtOAc
  5. washthe combined organic phases were washed consecutively with 0.5 M aqueous dipotassium hydrogen phosphate and brine
  6. concentrationconcentrated
  7. custompurified by HPLC [Waters Nova-Pak HR C18 column (25 mm×100 mm, 6 μm particle size)
  8. customover 8 min
  9. custom(10 min run time)

Sources & evidence

ORD record
ord-27f946d0159d48d9bba75ac3e4d86969
Source dataset
uspto-grants-2009_05
Patent number
US07538138B2

Reaction notes

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