Dimethylformamide → HCID 86660253, compound

HRID 2204087Notes

Reaction equation

HRID 2204087 reaction equation
O=P(Cl)(Cl)Cl.[Cl:6][C:7]1[CH:30]=[CH:29][C:10]2[N:11]3[CH:28]=[CH:27][CH:26]=[C:12]3[C:13]3([CH2:19][CH2:18][N:17]([C:20](=[O:25])[C:21]([F:24])([F:23])[F:22])[CH2:16][CH2:15]3)[O:14][C:9]=2[CH:8]=1.CN([CH:34]=[O:35])C>>[Cl:6][C:7]1[CH:30]=[CH:29][C:10]2[N:11]3[C:28]([CH:34]=[O:35])=[CH:27][CH:26]=[C:12]3[C:13]3([CH2:15][CH2:16][N:17]([C:20](=[O:25])[C:21]([F:23])([F:24])[F:22])[CH2:18][CH2:19]3)[O:14][C:9]=2[CH:8]=1

Participants

4

Reactant 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 58551284HCID 58551284, compound

Product 1

HCID 86660253HCID 86660253, compound

Procedure

POCl3 (1.33 mL, 14.3 mmol) was added dropwise at 0° C. under N2 to dry DMF (1.1 mL, 14 mmol). The reaction mixture was left for 20 min at this temperature, which led to the formation of a white solid. A solution of 1-(7′-chlorospiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl)-2,2,2-trifluoro-ethanone (353 mg, 9.535 mmol) in dry DMF (26.5 mL) was added dropwise and the cooling bath was removed. The reaction was allowed to stir at room temperature for 1 h. The mixture was poured over ice and 1M NaOH (25 ml) was added. The pH was adjusted to 7 with 3M HCl and the mixture was extracted with DCM three times. The combined organics were dried, filtered and concentrated. Column chromatography (5-30% AcOEt in hexanes) on the residue gave 7-chloro-1′-(2,2,2-trifluoroacetyl)spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1-carbaldehyde. ESI-MS m/z calc. 398.1, found 399.3 (M+1)+; Retention time: 1.96 minutes (3 min run).

Workup

  1. customthe cooling bath was removed
  2. additionThe mixture was poured over ice and 1M NaOH (25 ml)
  3. additionwas added
  4. extractionthe mixture was extracted with DCM three times
  5. customThe combined organics were dried
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-f7550394ab2b4d8b90997d932a468e48
Source dataset
uspto-grants-2016_06
Patent number
US09365588B2

Reaction notes

Loading…