Formaldehyde → 3-(4-Methoxybenzyl)6,7-difluor-2,3-dihydrobenzo[e][1,3]oxazin-4-one

HRID 1271051Notes

Reaction equation

HRID 1271051 reaction equation
[C:1]1(C)C=CC=CC=1.[CH3:8][O:9][C:10]1[CH:28]=[CH:27][C:13]([CH2:14][NH:15][C:16](=[O:26])[C:17]2[CH:22]=[C:21]([F:23])[C:20]([F:24])=[CH:19][C:18]=2[OH:25])=[CH:12][CH:11]=1.C=O.C(=O)(O)[O-].[Na+]>C1(C)C=CC(S(O)(=O)=O)=CC=1.O>[CH3:8][O:9][C:10]1[CH:11]=[CH:12][C:13]([CH2:14][N:15]2[C:16](=[O:26])[C:17]3[CH:22]=[C:21]([F:23])[C:20]([F:24])=[CH:19][C:18]=3[O:25][CH2:1]2)=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 1140TolueneHCID 516892Sodium BicarbonateHCID 18452522N-(4-methoxybenzyl)-4,5-difluoro-2-hydroxybenzamide

Product 1

HCID 184524873-(4-Methoxybenzyl)6,7-difluor-2,3-dihydrobenzo[e][1,3]oxazin-4-oneYield 86%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 962WaterSolvent

Procedure

To a toluene solution (25 mL) of N-(4-methoxybenzyl)-4,5-difluoro-2-hydroxybenzamide (1.5 g, 5 mmol) was added paraformaldehyde (0.450 g, 15 mmol) and para-toluenesulfonic acid (0.01 g, 0.05 mmol) and the reaction heated to 110° C. for 3 hr with azeotropic removal of water. Saturated sodium bicarbonate (50 ml) was added and product extracted with ethyl acetate, dried over anhydrous sodium sulfate and concentrated to give 1.3 g (86%) of 3-(4-methoxybenzyl)6,7-difluor-2,3-dihydrobenzo[e][1,3]oxazin-4-one. RP-HPLC: 2.64 min; ES-MS (M+H)+=307.0; 1H-NMR (MeOH-d4) δ (ppm): 7.8 (dd, 1 H), 7.4 (d, 2 H), 6.8 (d, 2 H), 5.1 (s, 2 H), 4.6 (s, 2 H), 3.8 (s, 3 H).

Workup

  1. extractionproduct extracted with ethyl acetate
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-71ed1fe7e2f54813965d8966d035de9f
Source dataset
uspto-grants-2007_04
Patent number
US07205296B2

Reaction notes

Loading…