1,2-Dimethoxyethane → HCID 59594384, compound

HRID 2263688Notes

Reaction equation

HRID 2263688 reaction equation
Cl[C:2]1[C:3]2[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:4]=2[N:5]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[C:6](=[O:9])[CH2:7][N:8]=1.COCCOC.C([O-])([O-])=O.[Na+].[Na+].[CH3:36][O:37][C:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=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.CCCCCCC.CCOC(C)=O>[Cl:23][C:21]1[CH:20]=[CH:19][C:4]2[N:5]([CH2:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)[C:6](=[O:9])[CH2:7][N:8]=[C:2]([C:41]3[CH:42]=[CH:43][C:38]([O:37][CH3:36])=[CH:39][CH:40]=3)[C:3]=2[CH:22]=1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 59594371HCID 59594371, compound

Product 1

HCID 59594384HCID 59594384, compoundYield 33.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 21899848Ethylacetate heptaneSolvent

Conditions

Temperature
85 °C

Procedure

In a 1 L 3 neck RBF equipped with magnetic stir bar, condenser, thermocouple, and N2 inlet, crude (E)-5,7-dichloro-1-(4-methoxybenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (54 g) was dissolved into 360 mL of DME. To this was added a solution of Na2CO3 (23 g, 0.15 mol, in 250 mL of H2O) followed by the addition of 4-methoxyphenyl boronic acid (22.7 g, 0.15 mol) and Pd(PPh3)4 (1.4 g, 1.2 mmol). The reaction mixture was heated in a 85° C. oil bath for 2 h and then cooled (RT). To this was added 200 mL of EtOAc and the mixture stirred for 5 min. Organic layer was separated and washed with 200 mL H2O and then brine. Organic layer was concentrated to dryness to give 68 g of crude product. This was subjected to column chromatography using 550 g of silica gel and 25/75 to 60/40 EtOAc/heptane. Fractions containing pure product were combined to give 21 g of pure product and other fractions containing a small amount of impurity (by TLC) gave another 20 g of product, albeit less pure. However NMR of both lots was identical. Total of 41 g of product was obtained. Yield 72% over two steps. 1H NMR (300 MHz, CDCl3) δ 3.7 (s, 3H), 3.80 (d, 1H), 3.85 (s, 3H), 4.57 (d, 1H), 4.85 (d, 1H), 5.57 (d, 1H), 6.63 (d, 2H), 6.85-6.95 (m, 4H), 7.16 (d, 1H), 7.3-7.44 (m, 4H).

Workup

  1. temperaturecooled (RT)
  2. customOrganic layer was separated
  3. washwashed with 200 mL H2O
  4. concentrationOrganic layer was concentrated to dryness
  5. customto give 68 g of crude product
  6. additionFractions containing pure product

Sources & evidence

ORD record
ord-e6a65fce784341e8ab24cef6fc6a28fc
Source dataset
uspto-grants-2010_12
Patent number
US07851465B2

Reaction notes

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