Hydrochloric Acid → HCID 11694979, compound

HRID 2103050Notes

Reaction equation

HRID 2103050 reaction equation
C([O:4][C:5]1[C:6]([CH3:22])=[C:7]2[C:15](=[CH:16][C:17]=1[CH:18]([CH3:20])[CH3:19])[O:14][C:10]1([CH2:13][CH2:12][CH2:11]1)[CH2:9][C:8]2=O)(=O)C.Cl.[CH3:24][O:25][NH2:26].Cl>CO.C(OCC)(=O)C.O1CCCC1>[CH:18]([C:17]1[CH:16]=[C:15]2[C:7]([CH:8]([NH:26][O:25][CH3:24])[CH2:9][C:10]3([O:14]2)[CH2:13][CH2:12][CH2:11]3)=[C:6]([CH3:22])[C:5]=1[OH:4])([CH3:20])[CH3:19]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 521874O-Methylhydroxylamine hydrochlorideHCID 69053183HCID 69053183, compound

Product 1

HCID 11694979HCID 11694979, compoundYield 59.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
100 °C

Procedure

A mixture of 7-isopropyl-5-methyl-4-oxospiro[chroman-2,1′-cyclobutane]-6-yl acetate (1.0 g) and methoxyamine hydrochloride (1.0 g) in methanol (3 mL) was microwave heated at 60° C. for 3 min., 100° C. for 5 min., and 120° C. for 10 min. Two runs (total 2 g, 6.62 mmol) were combined. The solution was diluted with ethyl acetate and washed with water and brine. The crude product obtained (6.62 mmol) was dissolved in tetrahydrofuran (5 mL) and borane-pyridine complex (4 mL) at 0° C. followed by hydrogen chloride (8 mL, 4.0 M solution in dioxane) were added for 50 minutes. The solution was allowed to warm to room temperature slowly. After 48 hours, ethyl acetate was added. The solution was washed with saturated sodium bicarbonate water solution, water and brine. Evaporation and chromatography (silica gel, hexane-ethyl acetate 1% to 8%) gave 573 mg of 7-isopropyl-4-(methoxyamino)-5-methylspiro[chroman-2,1′-cyclobutan]-6-ol. 1H-NMR (300 MHz, CDCl3) δ=6.63 (s, 1H), 4.54 (s, 1H), 5.35 (s, 1H), 4.30-4.25 (m, 1H), 3.65 (s, 3H), 3.15-3.10 (m, 1H), 2.70-2.60 (m, 2H), 2.40-2.10 (m, 6H), 2.10-1.75 (m, 3H), 1.22 (d, J=6.7 Hz, 6H) ppm. 13C-NMR (75 MHz, CDCl3) δ=148.4, 144.9, 136.1, 123.0, 115.2,112.4, 76.7, 61.9, 52.6, 35.7, 34.4, 32.5, 27.3, 22.7, 22.6, 13.7, 11.5 ppm. MS (m/z)=245 (100, M+H+−18).

Workup

  1. washwashed with water and brine
  2. customThe crude product obtained (6.62 mmol)
  3. customat 0° C.
  4. additionwere added for 50 minutes
  5. temperatureto warm to room temperature slowly
  6. waitAfter 48 hours
  7. washThe solution was washed with saturated sodium bicarbonate water solution, water and brine
  8. customEvaporation and chromatography (silica gel, hexane-ethyl acetate 1% to 8%)

Sources & evidence

ORD record
ord-429c954d6cb44a9fa8fc1f6f8bf6dcca
Source dataset
uspto-grants-2009_08
Patent number
US07576094B2

Reaction notes

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