Acetic Anhydride → HCID 58550817, compound

HRID 1908168Notes

Reaction equation

HRID 1908168 reaction equation
C(OC(=O)C)(=O)C.[CH2:8]([C:10]1[CH:38]=[CH:37][C:13]([C:14]([N:16]2[CH2:21][CH2:20][C:19]3([O:26][C:25]4[CH:27]=[CH:28][CH:29]=[CH:30][C:24]=4[N:23]4[C:31](/[CH:34]=[N:35]\O)=[CH:32][CH:33]=[C:22]34)[CH2:18][CH2:17]2)=[O:15])=[CH:12][C:11]=1[O:39][CH3:40])[CH3:9].C(=O)(O)[O-].[Na+]>ClCCl>[CH2:8]([C:10]1[CH:38]=[CH:37][C:13]([C:14]([N:16]2[CH2:17][CH2:18][C:19]3([O:26][C:25]4[CH:27]=[CH:28][CH:29]=[CH:30][C:24]=4[N:23]4[C:31]([C:34]#[N:35])=[CH:32][CH:33]=[C:22]34)[CH2:20][CH2:21]2)=[O:15])=[CH:12][C:11]=1[O:39][CH3:40])[CH3:9]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 516892Sodium BicarbonateHCID 58551635HCID 58551635, compound

Product 1

HCID 58550817HCID 58550817, compoundYield 116.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
140 °C

Procedure

Acetic anhydride (4.0 mL, 42 mmol) was added to (Z)-1′-(4-ethyl-3-methoxybenzoyl)spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1-carbaldehyde oxime (847 mg from previous step). The reaction mixture was heated at 140° C. for 3.5 h then cooled to room temperature and poured onto ice. Dichloromethane (30 mL) was added followed by sodium bicarbonate (0.7 g). The organic phase was then separated and the aqueous layer was extracted twice with dichloromethane. The combined organic layers were washed with brine, dried, filtered, and concentrated to give a yellow oil. The crude material was purified by column chromatography (silica gel: 5-45% EtOAc in hexanes) to give 1′-(4-ethyl-3-methoxybenzoyl)spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1-carbonitrile (944 mg, 69%). 1H NMR (400 MHz, CDCl3) δ 8.10 (d, J=8.0 Hz, 1H), 7.22-7.16 (m, 1H), 7.15-7.08 (m, J=7.6 Hz, 3H), 7.00 (d, J=4.0 Hz, 1H), 6.93-6.87 (m, 2H), 6.08 (d, J=4.0 Hz, 1H), 4.64 (s, 1H), 3.83 (s, 3H), 3.65-3.14 (m, 3H), 2.62 (q, J=7.5 Hz, 2H), 2.27-1.67 (m, 4H), 1.16 (t, J=7.5 Hz, 3H). ESI-MS m/z calc. 427.5. found 428.5 (M+1)+; Retention time: 2.08 minutes (3 min run).

Workup

  1. temperaturethen cooled to room temperature
  2. additionpoured onto ice
  3. customThe organic phase was then separated
  4. extractionthe aqueous layer was extracted twice with dichloromethane
  5. washThe combined organic layers were washed with brine
  6. customdried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a yellow oil
  10. customThe crude material was purified by column chromatography (silica gel: 5-45% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c254d9cd285a468d8325f144b2f8c1e6
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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