tert-Butyl acrylate → HCID 89602354, compound

HRID 2174582Notes

Reaction equation

HRID 2174582 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:17])[CH2:10][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[N:6][CH:7]=1.[C:18]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])(=[O:21])[CH:19]=[CH2:20].CCN(C(C)C)C(C)C>>[O:14]1[CH2:15][CH2:16][N:11]([CH2:10][C:9]([NH:8][C:5]2[N:6]=[CH:7][C:2](/[CH:20]=[CH:19]/[C:18]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[CH:3][CH:4]=2)=[O:17])[CH2:12][CH2:13]1

Participants

4

Reactant 3

HCID 15458tert-Butyl acrylateHCID 81531DiisopropylethylamineHCID 1237386HCID 1237386, compound

Product 1

HCID 89602354HCID 89602354, compoundYield 75.3%

Conditions

Temperature
105 °C

Procedure

A solution of 58b (640 mg, 2.14 mmol), tert-butyl acrylate (1.37 g, 10.7 mmol), DIPEA (0.74 ml, 4.28 mmol), Pd-(OAc)2 (47 mg, 0.21 mmol) and P (o-tol)3 (129 mg, 0.42 mmol) in propionitrile (8 ml) and DMF (2 ml) was purged with nitrogen for 10 minutes, and then was heated at 100-110° C. for 16 h. The progress of the reaction was monitored by TLC. After 16 h of stirring, the reaction mixture was cooled to 20-35° C., filtered through celite, and then concentrated. The resultant residue was diluted with water (50 ml) and extracted with ethyl acetate (2×50 ml). The combine organic layers were washed with brine (50 ml), followed by drying over anhydrous Na2SO4 and filtering. The filtrate was rotary evaporated to get residue which was purified by column chromatography using a mixture of 60% ethyl acetate/pet ether as an eluent to get the desired compound as an off-white solid (560 mg, 75%). 1H NMR (400 MHz, DMSO-d6) δ 10.17 (s, 1H), 8.60 (d, J=2.0 Hz, 1H), 8.20 (dd, J=8.8, 2.5 Hz, 1H), 8.11 (d, J=8.8 Hz, 1H), 7.53 (d, J=16.1 Hz, 1H), 6.56 (d, J=16.2 Hz, 1H), 3.62 (t, J=4.4 Hz, 4H), 3.21 (s, 2H), 2.55-2.51 (m, 4H), 1.48 (s, 9H); MS (ES) m/e 348.0 (M+H)+.

Workup

  1. custom(129 mg, 0.42 mmol) in propionitrile (8 ml) and DMF (2 ml) was purged with nitrogen for 10 minutes
  2. temperaturethe reaction mixture was cooled to 20-35° C.
  3. filtrationfiltered through celite
  4. concentrationconcentrated
  5. additionThe resultant residue was diluted with water (50 ml)
  6. extractionextracted with ethyl acetate (2×50 ml)
  7. washThe combine organic layers were washed with brine (50 ml)
  8. dry with materialby drying over anhydrous Na2SO4
  9. filtrationfiltering
  10. customThe filtrate was rotary evaporated
  11. customto get residue which
  12. customwas purified by column chromatography
  13. additiona mixture of 60% ethyl acetate/pet ether as an eluent

Sources & evidence

ORD record
ord-b99f0a277ed7487a93f1f39cce05ea40
Source dataset
uspto-grants-2015_06
Patent number
US09062002B2

Reaction notes

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