Water → 4-Chloro-6-methyl-2-[4-(2-methyl-benzyl)-piperazin-1-yl]-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

HRID 1927500Notes

Reaction equation

HRID 1927500 reaction equation
[C:1]1([CH3:9])[C:2]([CH:7]=O)=[CH:3][CH:4]=[CH:5][CH:6]=1.[CH3:10][O:11][C:12]([C:14]1[CH:15]=[C:16]([CH3:38])[C:17]2[O:23][C:22]3[C:24]([Cl:34])=[CH:25][C:26]([N:28]4[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]4)=[CH:27][C:21]=3[CH2:20][S:19](=[O:36])(=[O:35])[C:18]=2[CH:37]=1)=[O:13].C([BH3-])#N.[Na+].O>CO.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH3:10][O:11][C:12]([C:14]1[CH:15]=[C:16]([CH3:38])[C:17]2[O:23][C:22]3[C:24]([Cl:34])=[CH:25][C:26]([N:28]4[CH2:29][CH2:30][N:31]([CH2:9][C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=5[CH3:7])[CH2:32][CH2:33]4)=[CH:27][C:21]=3[CH2:20][S:19](=[O:35])(=[O:36])[C:18]=2[CH:37]=1)=[O:13]

Participants

7

Reactant 4

HCID 962WaterHCID 107222-MethylbenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 115410724-Chloro-6-methyl-10,10-dioxo-2-piperazin-1-yl-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclo heptene-8-carboxylic acid methyl ester

Product 1

HCID 1317284824-Chloro-6-methyl-2-[4-(2-methyl-benzyl)-piperazin-1-yl]-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

o-Tolualdehyde (0.041 mL, 0.35 mmol) and titanium isopropoxide (0.136 mL, 0.45 mmol) were added to a suspension of Example 104k (0.16 g, 0.36 mmol) in methanol (7 mL). The reaction mixture was stirred at 70° C. for 1.5 h, cooled to room temperature, treated with sodium cyanoborohydride (0.022 g, 0.34 mmol), then stirred at 70° C. for 1 h and at room temperature overnight. It was treated with water and extracted with n-butanol. The organic layer was washed with water, brine, dried, concentrated and purified using flash chromatography (silica gel, ethyl acetate/pet ether) to obtain the title compound. Yield: 0.060 g, (30%); 1H NMR (CDCl3): δ 2.4 (s, 3H, CH3), 2.6 (t, 4H, 2CH2), 2.71 (s, 3H, CH3), 3.21 (t, 4H, 2CH2), 3.53 (s, 2H, CH2), 3.92 (s, 3H, OCH3), 4.67 (s, 2H, CH2), 6.74 (d, 1H, Ar), 6.88 (d, 1H, Ar), 7.13 (t, 1H, Ar), 8.07 (d, 1H, Ar), 8.43 (d, 1H, Ar); MS: m/e (ES+) 542 (M+1).

Workup

  1. temperaturecooled to room temperature
  2. stirringstirred at 70° C. for 1 h and at room temperature overnight
  3. extractionextracted with n-butanol
  4. washThe organic layer was washed with water, brine
  5. customdried
  6. concentrationconcentrated
  7. custompurified

Sources & evidence

ORD record
ord-deeb172dc81d4952999a77b665217216
Source dataset
uspto-grants-2012_05
Patent number
US08183234B2

Reaction notes

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