Dimethylformamide → HCID 58551582, compound

HRID 1908064Notes

Reaction equation

HRID 1908064 reaction equation
O=P(Cl)(Cl)Cl.[F:6][C:7]([F:30])([F:29])[C:8]([N:10]1[CH2:28][CH2:27][C:13]2([C:18]3=[C:19]([CH3:22])[CH:20]=[CH:21][N:17]3[C:16]3[CH:23]=[CH:24][CH:25]=[CH:26][C:15]=3[O:14]2)[CH2:12][CH2:11]1)=[O:9].[OH-].[Na+].CN([CH:36]=[O:37])C>>[CH3:22][C:19]1[CH:20]=[C:21]([CH:36]=[O:37])[N:17]2[C:18]=1[C:13]1([CH2:27][CH2:28][N:10]([C:8](=[O:9])[C:7]([F:6])([F:29])[F:30])[CH2:11][CH2:12]1)[O:14][C:15]1[CH:26]=[CH:25][CH:24]=[CH:23][C:16]2=1

Participants

5

Reactant 4

HCID 6228Dimethylformamide2×HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 58550965HCID 58550965, compound

Product 1

HCID 58551582HCID 58551582, compoundYield 24%

Procedure

POCl3 (38 μL, 0.41 mmol) was added dropwise at 0° C. under N2 to DMF (32 μL, 0.41 mmol). The reaction was stirred for 30 min at this temperature and a white solid formed, to which was slowly added a solution of 2,2,2-trifluoro-1-(3′-methylspiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl)ethanone (95 mg, 0.27 mmol) in dry DMF (0.7 mL). The reaction stirred for 4 h, poured onto ice, 0.8 ml of 1M NaOH was added and the product was extracted with dichloromethane (3×5 mL). The organic phases were combined, washed with brine, dried, filtered and concentrated and the residue was purified by silica-gel column chromatography eluting with 5-40% EtOAc in hexanes to yield 3-methyl-1′-(2,2,2-trifluoroacetyl)spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1-carbaldehyde (25 mg, 24%). ESI-MS m/z calc. 378.1. found 379.3 (M+1)+; Retention time 1.83 minutes (3 min run).

Workup

  1. customa white solid formed, to which
  2. stirringThe reaction stirred for 4 h
  3. additionwas added
  4. extractionthe product was extracted with dichloromethane (3×5 mL)
  5. washwashed with brine
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customthe residue was purified by silica-gel column chromatography
  10. washeluting with 5-40% EtOAc in hexanes

Sources & evidence

ORD record
ord-8c3f568b6f244c8baf5c7431673ad189
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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