Ethanol → HCID 69872870, compound

HRID 398131Notes

Reaction equation

HRID 398131 reaction equation
[CH2:1]([O:3][C:4](=[O:31])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:29]=[CH:28][C:27](Br)=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][CH:10]=1)([CH3:7])[CH3:6])[CH3:2].[C:32]([O:36][C:37]([N:39]1[CH:43]=[CH:42][CH:41]=[C:40]1B(O)O)=[O:38])([CH3:35])([CH3:34])[CH3:33].C(O)C.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=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.C(OCC)(=O)C>[C:32]([O:36][C:37]([N:39]1[CH:43]=[CH:42][CH:41]=[C:40]1[C:27]1[CH:28]=[CH:29][C:24]([C:20]2[O:21][C:22]([CH3:23])=[C:18]([CH2:17][CH2:16][O:15][C:12]3[CH:13]=[CH:14][C:9]([O:8][C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:31])([CH3:7])[CH3:6])=[CH:10][CH:11]=3)[N:19]=2)=[CH:25][CH:26]=1)=[O:38])([CH3:35])([CH3:33])[CH3:34]

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27343211-(tert-Butoxycarbonyl)-2-pyrroleboronic AcidHCID 110273422-(4-{2-[2-(4-Bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methylpropionic acid ethyl ester

Product 1

HCID 69872870HCID 69872870, compoundYield 92%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-(4-{2-[2-(4-bromophenyl)-5-methyloxazol-4-yl]ethoxy}phenoxy)-2-methyl-propionic acid ethyl ester (907 mmol) (see Ex. 2, part B) and 1-(t-butoxycarbonyl)pyrrole-2-boronic acid (0.998 mmol) in toluene:ethanol (18.2 mL of a 1:1 solution) was treated with Na2CO3 (aq) (0.906 mL of a 2M solution). A nitrogen atmosphere was applied, Pd(PPh3)4 (52.5 mg) was added, and the orange mixture was heated at reflux for 2 h. After cooling to room temperature, the mixture was partitioned between ethyl acetate (20 mL) and H2O (30 mL). The layers were separated, and the aqueous phase was back-extracted with ethyl acetate (2×10 mL). Combined organic phases were washed with brine (20 mL), dried over Na2SO4, and concentrated. The product was purified by silica gel chromatography (20 g SiO2, 3:7 ethyl acetate:hexanes) to yield the product in 92% yield as an oil; Rf=0.50 in 1:4 ethyl acetate:hexanes; 1H NMR (400 MHz, CDCl3) δ7.92 (d, J=8.0 Hz, 2H), 7.37 (d, J=8.0 Hz, 2H), 7.34 (t, J=2.4 Hz, 1H), 6.79 (d, J=9.4 Hz, 2H), 6.74 (d, J=9.4 Hz, 2H), 6.21 (d, J=2.4 Hz, 2H), 4.20 (q, J=6.8 Hz, 2H), 4.16 (t, J=6.8 Hz, 2H), 2.93 (d, J=6.8 Hz, 2H), 2.34 (s, 3H), 1.49 (s, 6H), 1.33 (s, 9H), MS (EI) 598.2 (M+Na)+, 575.2 (M+H)+.

Workup

  1. temperaturethe orange mixture was heated
  2. temperatureat reflux for 2 h
  3. customthe mixture was partitioned between ethyl acetate (20 mL) and H2O (30 mL)
  4. customThe layers were separated
  5. extractionthe aqueous phase was back-extracted with ethyl acetate (2×10 mL)
  6. washCombined organic phases were washed with brine (20 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe product was purified by silica gel chromatography (20 g SiO2, 3:7 ethyl acetate:hexanes)
  10. customto yield the product in 92% yield as an oil

Sources & evidence

ORD record
ord-3fe9c296c9214a7b82e247120b5a1e7a
Source dataset
uspto-grants-2003_08
Patent number
US06610696B2

Reaction notes

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