[3-(Adamantan-1-yl)-4-(benzyloxy)phenyl]boronic acid → ethyl(E)-3-{2-[3-(1-adamantyl)-4-benzyloxyphenyl]-5-pyrazinyl}-2-propenoate

HRID 508662Notes

Reaction equation

HRID 508662 reaction equation
[C:1]12([C:11]3[CH:12]=[C:13](B(O)O)[CH:14]=[CH:15][C:16]=3[O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.Br[C:29]1[N:30]=[CH:31][C:32](/[CH:35]=[CH:36]/[C:37]([O:39][CH2:40][CH3:41])=[O:38])=[N:33][CH:34]=1>COCCOC.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:1]12([C:11]3[CH:12]=[C:13]([C:29]4[CH:34]=[N:33][C:32](/[CH:35]=[CH:36]/[C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:31][N:30]=4)[CH:14]=[CH:15][C:16]=3[O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2

Participants

5

Reactant 2

HCID 12134904[3-(Adamantan-1-yl)-4-(benzyloxy)phenyl]boronic acidHCID 53259408(E)-ethyl 3-(5-bromopyrazin-2-yl)acrylate

Product 1

HCID 53259588ethyl(E)-3-{2-[3-(1-adamantyl)-4-benzyloxyphenyl]-5-pyrazinyl}-2-propenoateYield 91.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 3-(1-adamantyl)-4-benzyloxyphenylboronic acid (474 mg, 1.31 mmol) and ethyl(E)-3-(5-bromo-2-pyrazinyl)-2-propenoate (278 mg, 1.08 mmol) in DME (11 mL, degassed) was added tetrakis(triphenylphosphine)palladium (151 mg, 0.13 mmol) and degassed 2 M Na2CO3 (2.3 mL). The reaction mixture was heated at reflux (90° C. oil-bath) for 19.5 h, cooled to room temperature, and then diluted with EtOAc (155 mL). The organic layer was washed (H2O and brine) and dried. After solvent removal at reduced pressure, the residue was purified on silica gel (10% to 25% EtOAc/hexane) to give 488 mg (91%) of ethyl(E)-3-{2-[3-(1-adamantyl)-4-benzyloxyphenyl]-5-pyrazinyl}-2-propenoate as a yellow solid, mp 145-148° C. IR 2899, 1710, 1238 cm−1; 1H NMR δ (CDCl3) 1.35 (t, J=7.3 Hz, 3H, OCH2CH3), 1.73 (bs, 6H, AdCH2), 2.06 (bs, 3H, AdCH), 2.20 (bs, 6H, AdCH2), 4.29 (q, J=7.3 Hz, 2H, OCH2CH3), 5.19 (s, 2H, CH2), 6.98 (d, J=15.9 Hz, 1H, CH═CHCO), 7.04 (d, J=8.5 Hz, 1H, 5-ArH), 7.28-7.52 (m, 5H, C6H5), 7.72 (d, J=15.9 Hz, 1H, CH═CHCO), 7.84 (dd, J=8.5 Hz, 2.4 Hz, 1H, 6-ArH), 8.02 (d, J=2.4 Hz, 1H, 2-ArH), 8.63 (d, J=1.24 Hz, 1H, 3-PyrH), 8.99 ppm (d, J=1.24 Hz, 1H, 6-PyrH). HRMS calcd C32H34N2O3 [M+H]+ 495.2642. found 495.2659.

Workup

  1. customdegassed 2 M Na2CO3 (2.3 mL)
  2. temperatureThe reaction mixture was heated
  3. temperaturecooled to room temperature
  4. additiondiluted with EtOAc (155 mL)
  5. washThe organic layer was washed (H2O and brine)
  6. customdried
  7. customAfter solvent removal at reduced pressure
  8. customthe residue was purified on silica gel (10% to 25% EtOAc/hexane)

Sources & evidence

ORD record
ord-38a9f136b4fe4fb693ed94e5753596ef
Source dataset
uspto-grants-2015_08
Patent number
US09096544B2

Reaction notes

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