Pyridine → tert-Butyl 5-(4-(4-bromophenyl)butanamido)-2-(ethylthio)benzyl(methyl)carbamate

HRID 735530Notes

Reaction equation

HRID 735530 reaction equation
C(Cl)(=O)[C:2](Cl)=[O:3].[Br:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]([CH2:18][CH3:19])C(O)=O)=[CH:10][CH:9]=1.[NH2:20][C:21]1[CH:22]=[CH:23][C:24]([S:37][CH2:38][CH3:39])=[C:25]([CH:36]=1)[CH2:26][N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31].N1C=CC=CC=1>C(Cl)Cl.CN(C=O)C.CN(C1C=CN=CC=1)C>[Br:7][C:8]1[CH:9]=[CH:10][C:11]([CH2:14][CH2:18][CH2:19][C:2]([NH:20][C:21]2[CH:22]=[CH:23][C:24]([S:37][CH2:38][CH3:39])=[C:25]([CH:36]=2)[CH2:26][N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:3])=[CH:12][CH:13]=1

Participants

8

Reactant 4

HCID 1049PyridineHCID 574722-(4-Bromophenyl)butanoic acidHCID 65578Oxalyl chlorideHCID 57956368tert-Butyl 5-amino-2-(ethylthio)benzyl(methyl)carbamate

Product 1

HCID 57956370tert-Butyl 5-(4-(4-bromophenyl)butanamido)-2-(ethylthio)benzyl(methyl)carbamateYield 88%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (0.180 mL, 2.06 mmol) was added dropwise to a suspension of 4-bromophenylbutanoic acid (0.250 g, 1.03 mmol) in DCM (3 mL) containing DMF (1 drop) at rt. After 4 h, the reaction mixture was concentrated in vacuo and coevaporated with toluene. The residue was dissolved in DCM (2 mL) and added dropwise to a solution of 17A (0.300 g, 1.01 mmol), DMAP (0.025 g, 0.2 mmol)and pyridine (1.0 mL, 12.3 mmol) in DCM (2 mL) at rt. The reaction mixture was stirred overnight at rt. The reaction mixture was concentrated in vacuo and the residue was triturated with water and then purified by silica gel chromatography (gradient from 0 to 20% ethyl acetate in hexanes) to give 17B (0.46 g, 88%) as a clear oil that solidified on standing. 1H NMR (400 MHz, CDCl3) δ ppm 1.26 (t, J=7.03 Hz, 3 H) 1.33-1.58 (m, 9 H) 1.96-2.04 (m, 2 H) 2.33 (t, J=7.47 Hz, 2 H) 2.63 (t, J=7.47 Hz, 2 H) 2.63 (t, J=7.47 Hz, 2 H) 2.74-2.93 (m, 3 H) 4.56 (br. s., 2 H) 6.96-7.02 (m, 0.5 H) 7.05 (d, J=8.35 Hz, 2 H) 7.13 (br. s., 0.4 H) 7.28-7.36 (m, 0.8 H) 7.38 (d, J=8.35 Hz, 2 H) 7.60-7.72 (m, 0.4 H) 7.81-7.98 (m, 0.9 H) 8.33 (br. s., 1 H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in DCM (2 mL)
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customthe residue was triturated with water
  5. custompurified by silica gel chromatography (gradient from 0 to 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-299951a814644dfe8887de927b87117a
Source dataset
uspto-grants-2009_09
Patent number
US07592331B2

Reaction notes

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