1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 22050189, compound

HRID 1867091Notes

Reaction equation

HRID 1867091 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[N:12]1[C:17]([CH3:18])=[CH:16][C:15]([OH:19])=[CH:14][C:13]1=[O:20].N12CCCN=C1CCCCC2.[F:32][C:33]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:34]=1[CH2:35]Br.C([O-])(O)=O.[Na+]>CN(C)C=O>[F:32][C:33]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:34]=1[CH2:35][O:19][C:15]1[CH:16]=[C:17]([CH3:18])[N:12]([C:3]2[CH:4]=[C:5]([CH:10]=[CH:11][C:2]=2[F:1])[C:6]([O:8][CH3:9])=[O:7])[C:13](=[O:20])[CH:14]=1

Participants

6

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 516892Sodium BicarbonateHCID 54724204HCID 54724204, compound

Product 1

HCID 22050189HCID 22050189, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 100 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with the product of Step 3 (14.4 g, 51.9 mmol) and N,N-dimethyl formamide (40 mL). 1,8-diazabicyclo[5.4.0]undec-7-ene (10.9 mL, 72.8 mmol) was added followed by 2,4-difluorobenzyl bromide (9.3 mL, 72.8 mmol). The reaction mixture was stirred at 65 C for 18 h, was poured into saturated aqueous NaHCO3 and was extracted with ethyl acetate. The organic layer was washed with brine, dried with Na2SO4 and concentrated in vacuo to give the title product, as an orange oil (21.59), which was carried on to the next reaction without further purification. 1H NMR (400 MHz, CD3OD) δ 8.20 (dddd, J=2.2, 4.8, 7.2 and 8.8 Hz, 1H), 8.00 (dd, J=2.2 and 7.2 Hz, 1H), 7.56 (td, J=2.4, 6.4 and 9.2 Hz, 1H), 7.46 (t, J=9.2 Hz, 1H), 7.02 (m, 2H), 6.18 (dd, J=0.8 and 2.6 Hz, 1H), 6.04 (d, J=2.7 Hz, 1H), 5.14 (s, 2H), 3.90 (s, 3H), 1.98 (s, 3H) ppm. 19F NMR (400 MHz, CD3OD) δ −111.34 (1F), −116.00 (1F), −117.35 (1F) ppm. ES-HRMS m/z 404.1104 (M+H calcd for C21H17F3NO4 requires 404.1104).

Workup

  1. customA 100 mL round bottomed flask equipped with stirbar and nitrogen inlet
  2. extractionwas extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-072203753674408fb5a6e642d01241c8
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

Loading…