Sodium hydride → Ethyl 9',10'-difluoro-7'-oxospiro[cyclobutane-1,3'(2'H)-[7H]pyrido[1,2,3-de][1,4]benzoxazine]-6'-carboxylate

HRID 444762Notes

Reaction equation

HRID 444762 reaction equation
[OH:1][CH2:2][C:3]1([NH:7][CH:8]=[C:9]([C:15](=[O:26])[C:16]2[CH:21]=[C:20]([F:22])[C:19]([F:23])=[C:18](F)[C:17]=2F)[C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:6][CH2:5][CH2:4]1.[H-].[Na+]>CN(C=O)C>[F:22][C:20]1[C:19]([F:23])=[C:18]2[O:1][CH2:2][C:3]3([CH2:6][CH2:5][CH2:4]3)[N:7]3[CH:8]=[C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:15](=[O:26])[C:16]([CH:21]=1)=[C:17]23

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 178471964HCID 178471964, compound

Product 1

HCID 58134828Ethyl 9',10'-difluoro-7'-oxospiro[cyclobutane-1,3'(2'H)-[7H]pyrido[1,2,3-de][1,4]benzoxazine]-6'-carboxylateYield 44.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of ethyl 3-[1-(hydroxymethyl)cyclobutylamino]-2-(2,3,4,5-tetrafluorobenzoyl)acrylate (1.52 g, 4.05 mmol) in DMF (10 mL) was added to an ice-cooled suspension of 60% NaH in oil (356 mg, 8.91 mmol) in DMF (10 mL), under argon atmosphere. The reaction mixture was stirred for 4 hours and poured into ice-water. The product was extracted with AcOEt, dried over MgSO4 and the crude product was purified by column chromatography (Hexane: EtOAc 2:1→AcOEt) to yield the title compound (604 mg, 44%) as a white solid. Mp 255-256° C. 1H-NMR (400 MHz, DMSO-d6) δ 1.29 (3H, t, J=7.3 Hz), 1.91-2.07 (2H, m), 2.16-2.22 (2H, m), 2.65-2.76 (2H, m), 4.24 (2H, q, J=7.3 Hz), 4.62 (2H, s), 7.62 (1H, dd, J=10.4, 7.9 Hz), 8.80 (1H, s). ESIMS (+): 336 [M+H]+.

Workup

  1. temperaturecooled
  2. extractionThe product was extracted with AcOEt
  3. dry with materialdried over MgSO4
  4. customthe crude product was purified by column chromatography (Hexane: EtOAc 2:1→AcOEt)

Sources & evidence

ORD record
ord-7bae6b69ff9344afa4fb3535d2a6d7a2
Source dataset
uspto-grants-2013_07
Patent number
US08476261B2

Reaction notes

Loading…