tert-Butyl acrylate → 3-(5,7,8,9-Tetrahydro-6-oxa-1,9-diaza-benzocyclohepten-3-yl)-acrylic acide tert-butyl ester

HRID 340830Notes

Reaction equation

HRID 340830 reaction equation
Br[C:2]1[CH:12]=[N:11][C:5]2[NH:6][CH2:7][CH2:8][O:9][CH2:10][C:4]=2[CH:3]=1.[C:13]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])(=[O:16])[CH:14]=[CH2:15].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].ClCCl>[C:18]([O:17][C:13](=[O:16])/[CH:14]=[CH:15]/[C:2]1[CH:12]=[N:11][C:5]2[NH:6][CH2:7][CH2:8][O:9][CH2:10][C:4]=2[CH:3]=1)([CH3:21])([CH3:20])[CH3:19]

Participants

8

Reactant 4

HCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 593328677-bromo-1H,2H,3H,5H-pyrido[2,3-e][1,4]oxazepine

Product 1

HCID 593328753-(5,7,8,9-Tetrahydro-6-oxa-1,9-diaza-benzocyclohepten-3-yl)-acrylic acide tert-butyl ester

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolventHCID 86641869DMF propionitrileSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 3-Bromo-5,7,8,9-tetrahydro-6-oxa-1,9-diaza-benzocycloheptene (0.5 g, 2.2 mmol), tert-butyl acrylate (1.6 mL, 10.9 mmol) and (i-Pr)2EtN (1.1 mL, 6.5 mmol) in proprionitrile/DMF (20 mL/5 ml) was de-oxygenated with Ar for 30 min. The mixture was treated with Pd(OAc)2 (49 mg, 0.22 mmol) and P(o-tol)3 (133 mg, 0.44 mmol) then heated to 100° C. for 16 h. The hot mixture was filtered through a pad of celite. The filtrate was diluted with H2O (100 ml) then extracted with dichloromethane (1×75 mL). The combined organic fractions were treated with brine (100 mL), dried Over Na2SO4 and concentrated to give a yellow residue. This was subjected to flash chromatography on silica gel using 1.3% methanol:dichloromethane. The appropriate fractions were collected and concentrated, to give a cream solid. Yield: 0.4 g (67%); 1H NMR (400 MHz, DMSO-d6) δ8.19 (d, J=2.1 Hz, 1H), 7.87 (d, J=2.1 Hz, 1H), 7.44 (d, J=16.0 Hz, 1H), 6.87 (br s, 1H), 6.33 (d, J=16.0 Hz, 1H), 4.50 (s, 2H), 3.75-3.72 (m, 2H), 3.22-3.20 (m, 2H), 1.47 (s, 9H); ESI MS m/z 277 [C15H20N2O3+H]+

Workup

  1. filtrationThe hot mixture was filtered through a pad of celite
  2. additionThe filtrate was diluted with H2O (100 ml)
  3. extractionthen extracted with dichloromethane (1×75 mL)
  4. additionThe combined organic fractions were treated with brine (100 mL)
  5. dry with materialdried Over Na2SO4
  6. concentrationconcentrated
  7. customto give a yellow residue
  8. customThe appropriate fractions were collected
  9. concentrationconcentrated
  10. customto give a cream solid

Sources & evidence

ORD record
ord-58fe5653781c42e7a5053c707fe4783b
Source dataset
uspto-grants-2014_11
Patent number
US08895545B2

Reaction notes

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