Dimethylformamide → HCID 58551192, compound

HRID 2204152Notes

Reaction equation

HRID 2204152 reaction equation
O=P(Cl)(Cl)Cl.CN([CH:9]=[O:10])C.[F:11][C:12]([F:35])([F:34])[C:13]([N:15]1[CH2:33][CH2:32][C:18]2([C:23]3=[CH:24][CH:25]=[CH:26][N:22]3[C:21]3[C:27]([F:31])=[CH:28][CH:29]=[CH:30][C:20]=3[O:19]2)[CH2:17][CH2:16]1)=[O:14]>>[F:31][C:27]1[C:21]2[N:22]3[C:26]([CH:9]=[O:10])=[CH:25][CH:24]=[C:23]3[C:18]3([CH2:17][CH2:16][N:15]([C:13](=[O:14])[C:12]([F:11])([F:34])[F:35])[CH2:33][CH2:32]3)[O:19][C:20]=2[CH:30]=[CH:29][CH:28]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 58550726HCID 58550726, compound

Product 1

HCID 58551192HCID 58551192, compoundYield 100.7%

Procedure

POCl3 (282 μL, 3.0 mmol) was added dropwise at 0° C. under N2 to dry DMF (234 μL, 3.0 mmol). The reaction mixture was left for 20 min at this temperature, which led to the formation of a white solid. A solution of 2,2,2-trifluoro-1-(9′-fluorospiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl)ethanone (715 mg, 2.0 mmol) dry DMF (5.4 mL) was added drop-wise and the cooling bath was removed. The reaction was poured over ice, 1M NaOH was added (5 mL), then the pH was adjusted to 7 with 2M HCl. The mixture was extracted with dichloromethane (3×10 mL). The organics were combined, dried with MgSO4, filtered and evaporated to yield a residue that was purified by silica-gel column chromatography eluting with 5-30% EtOAc in hexanes to yield 9-fluoro-1′-(2,2,2-trifluoroacetyl)spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1-carbaldehyde (770 mg, quant). ESI-MS m/z calc. 382.1, found 383.3 (M+1)+; Retention time 1.71 minutes (3 min run).

Workup

  1. customthe cooling bath was removed
  2. additionThe reaction was poured over ice, 1M NaOH
  3. additionwas added (5 mL)
  4. extractionThe mixture was extracted with dichloromethane (3×10 mL)
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customto yield a residue that
  9. customwas purified by silica-gel column chromatography
  10. washeluting with 5-30% EtOAc in hexanes

Sources & evidence

ORD record
ord-1e2ab434f029420ab9341f4f84a3bb1e
Source dataset
uspto-grants-2016_06
Patent number
US09365588B2

Reaction notes

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