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

HRID 1818624Notes

Reaction equation

HRID 1818624 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+].[C:30]([C:34]1[CH:41]=[CH:40][C:37]([CH2:38]Br)=[CH:36][CH:35]=1)([CH3:33])([CH3:32])[CH3:31]>CN(C=O)C>[C:30]([C:34]1[CH:35]=[CH:36][C:37]([CH2:38][N:7]2[C:8]3[C:4](=[CH:3][C:2]([Cl:1])=[CH:10][CH:9]=3)[CH:5]=[C:6]2[C:11]([CH:13]([CH2:25][CH2:26][CH3:27])[CH2:14][C:15]2[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][CH:16]=2)=[O:12])=[CH:40][CH:41]=1)([CH3:33])([CH3:31])[CH3:32]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 878361-(Bromomethyl)-4-(1,1-dimethylethyl)benzeneHCID 67482179Methyl 4-{(2rs)-2-[(5-chloro-1h-indol-2-yl)carbonyl]pentyl}benzoate

Product 1

HCID 67482286Methyl 4-((2rs)-2-{[1-(4-tert-butylbenzyl)-5-chloro-1h-indol-2-yl]carbonyl}pentyl)benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the title compound of Example 3 Step D (240 mg, 0.63 mmol) in DMF (2.5 mL) was added NaH (30 mg, 60% suspension in mineral oil, 0.75 mmol). After 15 min, 4-tert-butylbenzyl bromide (0.126 mL, 0.69 mmol) was added, and the resultant mixture was stirred for 1.5 h, whereupon it was quenched by addition of sat. aq. NH4Cl. 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 25%, then 25 to 100% EtOAc in hexanes) provided the title compound: LCMS B, tr=3.30 min, m/z 530.3 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 7.84 (d, J=8.5 Hz, 2H), 7.63 (d, J=2.0 Hz, 1H), 7.29-7.23 (m, 4H), 7.15 (d, J=8.0 Hz, 2H), 7.13 (s, 1H), 6.82 (d, J=8.5 Hz, 2H), 5.78 (ABq, J=16.0 Hz, Δν=71.0 Hz, 2H), 3.87 (s, 3H), 3.62 (dddd, J=8.5, 8.5, 5.5, 5.5 Hz, 1H), 3.08 (dd, J=14.0, 8.5 Hz, 1H), 2.78 (dd, J=14.0, 5.5 Hz, 1H), 1.76-1.70 (m, 1H), 1.52-1.45 (m, 1H), 1.26 (s, 9H), 1.23-1.18 (m, 2H), 0.81 (t, J=7.5 Hz, 3H).

Workup

  1. customwas quenched by addition of sat. aq. NH4Cl
  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 25%

Sources & evidence

ORD record
ord-5bd199c2d25b42279fe30656a4a05569
Source dataset
uspto-grants-2009_10
Patent number
US07598398B2

Reaction notes

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