Boron trifluoride etherate → HCID 58550804, compound

HRID 2204130Notes

Reaction equation

HRID 2204130 reaction equation
[CH:1]([O:8][CH2:9][CH3:10])([O:5][CH2:6][CH3:7])OCC.B(F)(F)F.CCOCC.[F:20][C:21]1[CH:22]=[C:23]2[C:40](=[CH:41][CH:42]=1)[O:39][C:26]1([CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]1)[CH2:25][C:24]2=[O:43].CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>ClCCl>[CH2:9]([O:8][CH:1]([O:5][CH2:6][CH3:7])[CH:25]1[C:26]2([CH2:27][CH2:28][N:29]([C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])[CH2:30][CH2:31]2)[O:39][C:40]2[C:23](=[CH:22][C:21]([F:20])=[CH:42][CH:41]=2)[C:24]1=[O:43])[CH3:10]

Participants

7

Reactant 5

HCID 8000Boron trifluoride etherateHCID 31214Ethyl orthoformateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 11759463tert-Butyl 6-fluoro-4-oxo-3,4-dihydro-1'H-spiro[1-benzopyran-2,4'-piperidine]-1'-carboxylate

Product 1

HCID 58550804HCID 58550804, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To triethyl orthoformate (20.2 mL, 121.5 mmol) in dry dichloromethane (115 mL) under argon at −10° C. was added drop-wise BF3.OEt2 (15.4 mL, 121.5 mmol). The solution was allowed to warm to 0° C. and was stirred for 10 minutes. After, the solution was cooled to −78° C. prior to the slow drop-wise addition of tert-butyl 6-fluoro-4-oxo-spiro[chromane-2,4′-piperidine]-1′-carboxylate (13.6 g, 40.5 mmol) in dichloromethane (10 mL). iPr2NEt (24.7 mL, 141.7 mmol) was added drop-wise over 30 minutes, and the mixture was slowly warmed to room temperature and was stirred at 25° C. for 2 hours. The reaction mixture was diluted with the addition of dichloromethane (200 mL) followed by saturated aqueous sodium bicarbonate solution (200 mL). The mixture was shaken in a separatory funnel and separated. The organic layer was washed with additional sodium bicarbonate solution (200 mL) and brine (200 mL). The organic layer was dried over sodium sulfate, filtered and concentrated to yield a residue that was purified by silica gel column chromatography (0-25% EtOAc/hexanes gradient) to give tert-butyl 3-(diethoxymethyl)-6-fluoro-4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (3.9 g, 22%). ESI-MS m/z calc. 437.2, found 438.7 (M+1)+. Retention time 2.14 minutes (3 min run).

Workup

  1. temperatureAfter, the solution was cooled to −78° C.
  2. temperaturethe mixture was slowly warmed to room temperature
  3. stirringwas stirred at 25° C. for 2 hours
  4. stirringThe mixture was shaken in a separatory funnel
  5. customseparated
  6. washThe organic layer was washed with additional sodium bicarbonate solution (200 mL) and brine (200 mL)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto yield a residue that
  11. customwas purified by silica gel column chromatography (0-25% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-80b91f4fcd3747a3b082c506820c119b
Source dataset
uspto-grants-2016_06
Patent number
US09365588B2

Reaction notes

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