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

HRID 1818622Notes

Reaction equation

HRID 1818622 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]([C:18](=[O:23])[CH2:19][CH2:20][CH2:21][CH3:22])=[CH:5]2.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:34][O:35][C:36]([C:38]1[CH:43]=[CH:42][C:41]([CH2:44]Br)=[CH:40][CH:39]=1)=[O:37].[NH4+].[Cl-]>C1COCC1>[CH2:11]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([Cl:1])=[CH:10][CH:9]=2)[CH:5]=[C:6]1[C:18]([CH:19]([CH2:20][CH2:21][CH3:22])[CH2:44][C:41]1[CH:42]=[CH:43][C:38]([C:36]([O:35][CH3:34])=[O:37])=[CH:39][CH:40]=1)=[O:23])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 256687Methyl 4-(bromomethyl)benzoateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 674823471-[5-Chloro-1-(phenylmethyl)-1h-indol-2-yl]pentan-1-one

Product 1

HCID 67482415Methyl 4-{(2rs)-2-[(1-benzyl-5-chloro-1h-indol-2-yl)carbonyl]pentyl}benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled (−78° C.) solution of the title compound of Example 3 Step B (1.50 g, 4.61 mmol) in THF (20 mL) was added KHMDS (13.8 mL, 0.5 M in toluene, 6.90 mmol). After 25 min, a solution of methyl 4-bromomethyl benzoate (1.27 g, 5.54 mmol) in THF (5 mL) was added, and the resultant mixture was allowed to warm slowly to room temperature over 4 h. The reaction mixture was then poured into sat. aq. NH4Cl, and the aqueous phase was extracted with EtOAc. The organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo: LCMS A, tr=4.52 min, m/z 474.2 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 7.84 (d, J=8.0 Hz, 2 h), 7.64-7.63 (m, 1H), 7.27-7.25 (m, 3H), 7.22-7.19 (m, 2H), 7.15 (d, J=8.0 Hz, 2H), 7.14 (s, 1H), 5.80 (ABq, J=16.0 Hz, Δν=61.8 Hz, 2H), 3.87 (s, 3H), 3.63-3.59 (m, 1H), 3.07 (dd, J=13.5, 8.5 Hz, 1H), 2.77 (dd, J=13.5, 6.0 Hz, 1H), 1.74-1.69 (m, 1H), 1.53-1.45 (m, 1H), 1.23-1.18 (m, 2H), 0.82 (t, J=7.5 Hz, 3H).

Workup

  1. extractionthe aqueous phase was extracted with EtOAc
  2. dry with materialThe organic phase was dried over anhydrous Na2SO4
  3. concentrationconcentrated in vacuo
  4. customLCMS A, tr=4.52 min, m/z 474.2 [M+H]+

Sources & evidence

ORD record
ord-594653cbf95f4092b05efb0ed12a5037
Source dataset
uspto-grants-2009_10
Patent number
US07598398B2

Reaction notes

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