Cesium hydroxide → (Z)-7-Chloro-5-(4-(4-methoxybenzyloxy)phenyl)-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one

HRID 2263701Notes

Reaction equation

HRID 2263701 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.[OH-].[Cs+].[CH3:18][O:19][C:20]1[CH:42]=[CH:41][C:23]([CH2:24][O:25][C:26]2[CH:31]=[CH:30][C:29](B3OC(C)(C)C(C)(C)O3)=[CH:28][CH:27]=2)=[CH:22][CH:21]=1>O1CCOCC1.O.C(OCC)(=O)C.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>[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:29]3[CH:28]=[CH:27][C:26]([O:25][CH2:24][C:23]4[CH:22]=[CH:21][C:20]([O:19][CH3:18])=[CH:42][CH:41]=4)=[CH:31][CH:30]=3)[C:3]=2[CH:14]=1

Participants

7

Reactant 3

HCID 62750Cesium hydroxideHCID 123385855,7-Dichloro-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-oneHCID 595943752-{4-[(4-Methoxyphenyl)methoxy]phenyl}-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 59594389(Z)-7-Chloro-5-(4-(4-methoxybenzyloxy)phenyl)-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

(E)-5,7-Dichloro-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one (5.00 g, 20.57 mmol), cesium hydroxide (6.91 g, 41.1 mmol), and 2-(4-(4-methoxybenzyloxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (9.10 g, 26.7 mmol) were dissolved in dioxane/water (100 mL/30 mL), and the mixture was subjected to vacuum followed by nitrogen gas. The de-gassing was repeated twice, and then tetrakis(triphenylphosphine)palladium (0) (475 mg, 0.41 mmol) was added. The reaction was then heated to 90° C. for 18 hours, and then cooled to room temperature. The crude mixture was diluted with ethyl acetate, and the organic solution was washed with water, then brine, and then dried over sodium sulfate, and concentrated. The crude product was vacuum pulled through a silica plug eluting with 6:4 ethyl acetate:hexanes. The filtrate was concentrated and then washed with methyl-tert-butyl ether. The product was collected as a light yellow solid by filtration (5.13 g, 59%). 1HNMR (300 MHz, CDCl3) δ 3.36 (s, 3H), 3.73 (d, 1H), 3.81 (s, 3H), 4.77 (d, 1H), 5.03 (s, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.27 (d, 1H), 7.32 (d, 1H), 7.36 (d, 2H), 7.49 (dd, 1H), 7.55 (d, 2H).

Workup

  1. temperaturecooled to room temperature
  2. washthe organic solution was washed with water
  3. dry with materialbrine, and then dried over sodium sulfate
  4. concentrationconcentrated
  5. washeluting with 6:4 ethyl acetate
  6. concentrationThe filtrate was concentrated
  7. washwashed with methyl-tert-butyl ether
  8. filtrationThe product was collected as a light yellow solid by filtration (5.13 g, 59%)

Sources & evidence

ORD record
ord-af6c9973cd97404ba2c83b1ee58de9c4
Source dataset
uspto-grants-2010_12
Patent number
US07851465B2

Reaction notes

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