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1,2-Dimethoxyethane → 7-Chloro-1,3-dihydro-5-(4-methoxyphenyl)-1-methyl-2H-1,4-benzodiazepin-2-one

HRID 1256202
Notes
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Reaction equation

HRID 1256202 reaction equation
Cl[C:2]1[C:3]2[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:4]=2[N:5]([CH3:10])[C:6](=[O:9])[CH2:7][N:8]=1.COCCOC.C([O-])([O-])=O.[Na+].[Na+].[CH3:28][O:29][C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(C)=O>[Cl:15][C:13]1[CH:12]=[CH:11][C:4]2[N:5]([CH3:10])[C:6](=[O:9])[CH2:7][N:8]=[C:2]([C:33]3[CH:34]=[CH:35][C:30]([O:29][CH3:28])=[CH:31][CH:32]=3)[C:3]=2[CH:14]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 123385855,7-Dichloro-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one

Product 1

HCID 30858187-Chloro-1,3-dihydro-5-(4-methoxyphenyl)-1-methyl-2H-1,4-benzodiazepin-2-oneYield 109.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
85 °C

Procedure

In a 1 L 3-neck RBF equipped with magnetic stir bar, condenser, thermocouple, and N2 inlet, crude D1 (30 g, 0.124 mol) was dissolved into 300 mL of ethylene glycol dimethyl ether (DME). To this was added a solution of Na2CO3 (21 g, 0.2 mol in 200 mL of H2O) followed by addition of 4-methoxyphenyl boronic acid (22 g, 0.145 mol) and Pd(PPh3)4 (1.2 g, 8.3 mmol). The reaction mixture was heated in a 85° C. oil bath, under N2, for 2 h and then cool to room temp. To this was added 200 mL of EtOAc and the mixture stirred for 5 min. The organic layer was separated and washed with H2O (200 mL) and brine (200 mL). The organic layer was dried over MgSO4 and then concentrated to dryness to give 53 g of crude product. This material was subjected to silica gel chromatography using 210 g of silica gel and EtOAc/hepatene (12:88 to 30:70 to 50:50 to 70:30; total of 8 L mobile phase). Fractions containing pure product were combined and concentrated to dryness to give 42.7 g of pure product in approximately quantitative yield. 1H NMR (300 MHz, CDCl3) δ 3.38 (s, 3H), 3.73 (d, 1H), 3.85 (s, 3H), 4.75 (d, 1H), 6.9 (m, 2H), 7.31 (m, 2H), 7.48-7.58 (m, 3H).

Workup

  1. customIn a 1 L 3-neck RBF equipped with magnetic stir bar, condenser
  2. temperaturecool to room temp
  3. customThe organic layer was separated
  4. washwashed with H2O (200 mL) and brine (200 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated to dryness
  7. customto give 53 g of crude product
  8. additionFractions containing pure product
  9. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-a4a9332c69c54bbdb84925eed36a8925
Source dataset
uspto-grants-2013_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08461153B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes