Triethylamine → 3-[4-Methyl-3-oxo-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylmethylene]-azetidine-1-carboxylic acid tert-butyl ester

HRID 519052Notes

Reaction equation

HRID 519052 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][C:15]=1[C:16]([F:19])([F:18])[F:17])[O:12][CH2:11][C:10]1[N:5]2[CH:6]([CH3:29])[C:7](=[O:28])[N:8]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[N:9]=1.[C:30]([O:34][C:35]([N:37]1[CH2:40][C:39](=[CH2:41])[CH2:38]1)=[O:36])([CH3:33])([CH3:32])[CH3:31].CC1C(P(C2C(C)=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.C(N(CC)CC)C>CC#N.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:30]([O:34][C:35]([N:37]1[CH2:40][C:39](=[CH:41][C:2]2[CH:3]=[C:4]3[C:13](=[CH:14][C:15]=2[C:16]([F:18])([F:17])[F:19])[O:12][CH2:11][C:10]2[N:5]3[CH:6]([CH3:29])[C:7](=[O:28])[N:8]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:25])([CH3:26])[CH3:27])[N:9]=2)[CH2:38]1)=[O:36])([CH3:33])([CH3:32])[CH3:31]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 55269097tert-Butyl 3-methylideneazetidine-1-carboxylateHCID 867273036-Bromo-4-methyl-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

Product 1

HCID 867274173-[4-Methyl-3-oxo-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylmethylene]-azetidine-1-carboxylic acid tert-butyl esterYield 20.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of 6-bromo-4-methyl-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Example #53, Step E, 0.30 g, 0.61 mmol), 3-methylene-azetidine-1-carboxylic acid tert-butyl ester (0.123 g, 0.73 mmol), Pd(OAc)2 (0.027 g, 0.12 mmol), tri-O-tolylphosphine (0.074 g, 0.24 mmol) and triethylamine (0.184 g, 1.82 mmol) in CH3CN (10 mL) was heated at 110° C. for 14 hr. The reaction mixture was cooled to ambient temperature and the solvent was removed in vacuo. The residue was purified by preparative TLC (eluting with 25% EtOAc in petroleum ether) to give 3-[4-methyl-3-oxo-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylmethylene]-azetidine-1-carboxylic acid tert-butyl ester (0.072 g, 20%) as a yellow solid. LC/MS (Table 1, Method 2) Rt=1.523 min.; MS m/z: 605 [M+23]+.

Workup

  1. customthe solvent was removed in vacuo
  2. customThe residue was purified by preparative TLC (eluting with 25% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-baf8b587bc354bf6a3bf81cd7772d2b8
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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