Ammonium Chloride → HCID 24763458, compound

HRID 556374Notes

Reaction equation

HRID 556374 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([CH:9]=[CH:10][CH:11]=1)[NH2:8])([CH3:4])([CH3:3])[CH3:2].C[Al](C)C.C([O:18][C:19]([C:21]1[C:22]2[CH:29]=[CH:28][C:27]([O:30][C:31]3[CH:36]=[CH:35][N:34]=[C:33]([CH2:37][O:38]C(=O)CCCCC)[N:32]=3)=[CH:26][C:23]=2[S:24][CH:25]=1)=O)C.[NH4+].[Cl-]>C1(C)C=CC=CC=1.C1COCC1.CCOC(C)=O.O>[C:1]([C:5]1[CH:6]=[C:7]([NH:8][C:19]([C:21]2[C:22]3[CH:29]=[CH:28][C:27]([O:30][C:31]4[CH:36]=[CH:35][N:34]=[C:33]([CH2:37][OH:38])[N:32]=4)=[CH:26][C:23]=3[S:24][CH:25]=2)=[O:18])[CH:9]=[CH:10][CH:11]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 4

HCID 25517Ammonium ChlorideHCID 793343-tert-ButylanilineHCID 16682925TrimethylaluminumHCID 57556450HCID 57556450, compound

Product 1

HCID 24763458HCID 24763458, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

In a dried vessel, 82 mg (0.55 mMol) 3-tert-butyl-aniline are dissolved in 8 ml toluene and cooled in an ice bath. Then 825 μl Me3Al (2 M in toluene; 1.65 mMol) are added via syringe. After 1¼ h at rt, a solution of 107 mg (0.25 mMol) 6-(2-hexanoyloxymethyl-pyrimidin-4-yloxy)-benzo[b]thiophene-3-carboxylic acid ethyl ester (Step 17.5) in 1 ml THF is added and the solution is stirred for 1 h in an oil bath of 110° C. The solution is cooled in an icebath and hydrolyzed with 16 ml of a sat. NH4Cl solution. After 15 min stirring, the mixture is diluted with EtOAc and water, the aq. phase separated off and extracted twice with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated. Chromatography (Combi Flash; hexane/EtOAc 9:1→1:1→EtOAc) gives the title compound: Anal. (+0.3H2O): C,H,N,S; MS: [M+1]+=434; TLC(hexane/EtOAc 1:2): Rf=0.31; 1H MNR (DMSO-d6): δ ppm 10.32 (s, HN), 8.67 (d, 1H), 8.58 (s, 1H), 8.46 (d, 1H), 8.03 (s, 1H), 7.76 (s, 1H), 7.68 (d, 1H), 7.35 (d, 1H), 7.28 (t, 1H), 7.15 (d, 1H), 6.98 (d, 1H), 5.18 (sb, HO), 4.41 (s, CH2), 1.31 (s, 9H).

Workup

  1. temperaturecooled in an ice bath
  2. waitAfter 1¼ h at rt
  3. stirringAfter 15 min stirring
  4. customthe aq. phase separated off
  5. extractionextracted twice with EtOAc
  6. washThe organic layers are washed with water and brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-b03050f2ca334a5fa3f650abba49f33b
Source dataset
uspto-grants-2011_11
Patent number
US08058276B2

Reaction notes

Loading…