Ethyl orthoformate → HCID 58550808, compound

HRID 2204090Notes

Reaction equation

HRID 2204090 reaction equation
[CH:1]([O:8][CH2:9][CH3:10])([O:5][CH2:6][CH3:7])OCC.[O:11]=[C:12]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[O:27][C:14]2([CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[CH2:13]1.C(N(C(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:13]1[C:14]2([CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[CH2:18][CH2:19]2)[O:27][C:28]2[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:12]1=[O:11])[CH3:10]

Participants

6

Reactant 4

HCID 31214Ethyl orthoformateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 40427565Tert-butyl 4-oxo-3,4-dihydrospiro[1-benzopyran-2,4'-piperidine]-1'-carboxylate

Product 1

HCID 58550808HCID 58550808, compoundYield 101%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To triethyl orthoformate (85 mL, 510 mmol) in dry dichloromethane (460 mL) under nitrogen at −10° C. was added dropwise BF3OEt2 (65 mL, 510 mmol). The solution was allowed to warm to 0° C. and was stirred for 10 minutes. The solution was cooled to −78° C. prior to the slow dropwise addition of tert-butyl 4-oxospiro[chromane-2,4′-piperidine]-1′-carboxylate (55 g, 170 mmol) in dichloromethane (25 mL). N-ethyl-N-isopropylpropan-2-amine (100 mL, 600 mmol) was added over a 30 minutes period, and the mixture was slowly warmed to 25° C. and was stirred at this temperature overnight. The reaction mixture was diluted with dichloromethane (500 mL) followed by saturated aqueous sodium bicarbonate solution (500 mL). The layers were separated, and the organic layer was washed with additional sodium bicarbonate (500 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (0-25% ethyl acetate in hexane) to provide tert-butyl 3-(diethoxymethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-1′-carboxylate (72 g, 91%) as an orange oil. ESI-MS m/z calc. 419.5, found 420.3 (M+1)+; Retention time: 2.50 minutes (3 min run).

Workup

  1. temperatureThe solution was cooled to −78° C.
  2. temperaturethe mixture was slowly warmed to 25° C.
  3. stirringwas stirred at this temperature overnight
  4. customThe layers were separated
  5. washthe organic layer was washed with additional sodium bicarbonate (500 mL)
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel column chromatography (0-25% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-dc6866283d0b41e6944738893d70cd2c
Source dataset
uspto-grants-2016_06
Patent number
US09365588B2

Reaction notes

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