Sodium hydride → Methyl 4-[(2rs)-2-({5-chloro-1-[4-(trifluoromethyl)benzyl]-1h-indol-2-yl}carbonyl)pentyl]benzoate

HRID 1818626Notes

Reaction equation

HRID 1818626 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([CH:13]([CH2:25][CH2:26][CH3:27])[CH2:14][C:15]1[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][CH:16]=1)=[O:12])=[CH:5]2.[H-].[Na+].[F:30][C:31]([F:41])([F:40])[C:32]1[CH:39]=[CH:38][C:35]([CH2:36]Br)=[CH:34][CH:33]=1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:36][C:35]1[CH:34]=[CH:33][C:32]([C:31]([F:30])([F:40])[F:41])=[CH:39][CH:38]=1)[C:6]([C:11]([CH:13]([CH2:25][CH2:26][CH3:27])[CH2:14][C:15]1[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][CH:16]=1)=[O:12])=[CH:5]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 67482179Methyl 4-{(2rs)-2-[(5-chloro-1h-indol-2-yl)carbonyl]pentyl}benzoate

Product 1

HCID 67482502Methyl 4-[(2rs)-2-({5-chloro-1-[4-(trifluoromethyl)benzyl]-1h-indol-2-yl}carbonyl)pentyl]benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of the title compound of Example 3 Step D (39.0 mg, 0.10 mmol) in DMF (1.0 mL) was added NaH (4.3 mg, 60% suspension in mineral oil, 0.11 mmol). After 10 min, a solution of 4-trifluoromethylbenzyl bromide (26.0 mg, 0.11 mmol) in DMF (0.5 mL) was added, and the reaction mixture was stirred for 18 h, whereupon it was quenched by addition of sat. aq. NaHCO3. The aqueous phase was extracted with EtOAc, and the organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 10%, then 10 to 100% EtOAc in hexanes) provided the title compound: LCMS A, tr=4.65 min, m/z 542.1 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 7.87 (d, J=8.5 Hz, 2H), 7.71 (d, J=1.5 Hz, 1H), 7.51 (d, J=8.5 Hz, 2H), 7.33-7.23 (m, 3H), 7.19 (d, J=8.5 Hz, 2H), 6.98 (d, J=8.0 Hz, 2H), 5.88 (ABq, J=16.5 Hz, Δν=86 Hz, 2H), 3.91 (s, 3H), 3.69 (dddd, J=9.0, 9.0, 5.5, 5.5 Hz, 1H), 3.10 (dd, J=13.5, 9.0 Hz, 1H), 2.85 (dd, J=13.5, 5.5 Hz, 1H), 1.79-1.74 (m, 2H), 1.58-1.53 (m, 2H), 0.92 (t, J=7.0 Hz, 3H).

Workup

  1. customwas quenched by addition of sat. aq. NaHCO3
  2. extractionThe aqueous phase was extracted with EtOAc
  3. dry with materialthe organic phase was dried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. customPurification by flash chromatography on silica gel (0 to 10%

Sources & evidence

ORD record
ord-7dfb7adf2b9d492593366a709abc963a
Source dataset
uspto-grants-2009_10
Patent number
US07598398B2

Reaction notes

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