Trifluoroacetic acid → HCID 58551304, compound

HRID 1908067Notes

Reaction equation

HRID 1908067 reaction equation
[F:1][C:2]1[C:3]([N:9]2[CH:13]=[CH:12][CH:11]=[CH:10]2)=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.O=[C:15]1[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]1.C(O)(C(F)(F)F)=O>ClCCl>[F:1][C:2]1[C:3]2[N:9]3[CH:13]=[CH:12][CH:11]=[C:10]3[C:15]3([CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[O:8][C:4]=2[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 58551451HCID 58551451, compound

Product 1

HCID 58551304HCID 58551304, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-Fluoro-2-(1H-pyrrol-1-yl)phenol (2.7 g, 16.6 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (3.3 g, 16.6 mmol) were dissolved in dry dichloromethane (53.6 mL). TFA (2.3 mL, 30.3 mmol) was added over 15 min and stirring was continued for 12 hours. Additional TFA (2.3 mL, 30.3 mmol) was added at 25° C. The reaction mixture was concentrated under vacuum and the residue diluted with dichloromethane (350 mL) then washed with 1M NaOH (2×50 ml), dried, filtered and evaporated to dryness. The resulting material was purified by silica gel chromatography eluting with 0.5-40% MeOH in dichloromethane to yield 9-fluorospiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine] (3.4 g, 86%). ESI-MS m/z calc. 258.1. found 259.1 (M+1)+; Retention time 0.90 minutes (3 min run).

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. additionthe residue diluted with dichloromethane (350 mL)
  3. washthen washed with 1M NaOH (2×50 ml)
  4. customdried
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe resulting material was purified by silica gel chromatography
  8. washeluting with 0.5-40% MeOH in dichloromethane

Sources & evidence

ORD record
ord-7282463850ed4d7f9b2955fffa03fa0a
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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