Diethyl Ether → HCID 67468545, compound

HRID 1908017Notes

Reaction equation

HRID 1908017 reaction equation
[H-].[Na+].[O:3]=[C:4]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[O:19][C:6]2([CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]2)[CH2:5]1.C[CH2:27][O:28]CC.C(OCC)=O>CO>[OH:28][CH:27]=[C:5]1[C:6]2([CH2:7][CH2:8][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:10][CH2:11]2)[O:19][C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:4]1=[O:3]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 8025Ethyl formateHCID 24758Sodium hydrideHCID 40427565Tert-butyl 4-oxo-3,4-dihydrospiro[1-benzopyran-2,4'-piperidine]-1'-carboxylate

Product 1

HCID 67468545HCID 67468545, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

NaH (1.89 g, 47.3 mmol) was added in small portions to a mixture of tert-butyl 4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (3.0 g, 9.5 mmol), Et2O (75 mL), and MeOH (120 μL) at rt. The mixture was allowed to stir for 1 h before ethyl formate (9.2 mL, 110 mmol) was added dropwise. The mixture was allowed to stir at 25° C. overnight before it was quenched with 1M aqueous HCl. The layers were separated and the aqueous layer was extracted with ethyl acetate (3×). The combined organics were washed with brine, dried over sodium sulfate, and concentrated in vacuo. Column chromatography (0-100% ethyl acetate in hexanes) provided tert-butyl 3-(hydroxymethylene)-4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (1.2 g, 36%) as a light yellow solid. ESI-MS m/z calc. 345.2. found 246.2 (M+1-Boc)+; Retention time: 2.62 minutes (4 min run). 1H NMR (400 MHz, CDCl3) δ 15.13 (d, J=8.3 Hz, 1H), 7.93 (d, J=8.1 Hz, 1H), 7.88 (dd, J=7.8, 1.5 Hz, 1H), 7.50-7.44 (m, 1H), 7.06 (t, J=7.5 Hz, 1H), 6.96 (d, J=8.2 Hz, 1H), 4.10-3.95 (m, 2H), 3.25-3.15 (m 2H), 2.15 (d, J=12.7 Hz, 2H), 1.80-1.66 (m, 2H), 1.47 (s, 9H).

Workup

  1. additionwas added dropwise
  2. customwas quenched with 1M aqueous HCl
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (3×)
  5. washThe combined organics were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-59615f24328c471780d679b03bd2e34f
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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