Trifluoroacetic acid → HCID 58551304, compound

HRID 2204151Notes

Reaction equation

HRID 2204151 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-248ed003bdc24ccab05cff257bf07341
Source dataset
uspto-grants-2016_06
Patent number
US09365588B2

Reaction notes

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