Ethyl Acetate → 6-Hydroxy-7,8-dimethyl-3,4-dihydrospiro[chromene-2,1'-cyclobutane]-5-carbaldehyde

HRID 2103038Notes

Reaction equation

[CH3:1][C:2]1[C:14]([CH3:15])=[C:13]2[C:5]([CH2:6][CH2:7][C:8]3([O:12]2)[CH2:11][CH2:10][CH2:9]3)=[CH:4][C:3]=1[OH:16].C[CH2:18][O:19]C(C)=O>C(C(C#N)=C1C=C(C=CC2C=CC(N(C)C)=CC=2)OC(C)=C1)#N.[Ti](Cl)(Cl)(Cl)Cl>[OH:16][C:3]1[C:2]([CH3:1])=[C:14]([CH3:15])[C:13]2[O:12][C:8]3([CH2:9][CH2:10][CH2:11]3)[CH2:7][CH2:6][C:5]=2[C:4]=1[CH:18]=[O:19]

Participants

Conditions

Temperature: 0 °C

Procedure

0.3 g of a solution of 7,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol (prepared as described herein) was dissolved in 20 mL of 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (DCM). The solution was flushed with Argon then cooled to 0° C. in an ice bath. 0.151 mL (1.4 mmol) of titanium tetrachloride was added followed by 0.149 mL (1.7 mmol, 1.2 eq) of α,α-dichloromethyl-methyl ether. The solution was stirred at 0° C. for 10 min, warmed to room temperature, and stirred overnight. After addition of EtOAc (50 mL), the solution was washed with water, and then dried over Na2SO4. The crude material was purified on a silica column eluting with 1:8 EtOAc/hexane to yield 180 mg of 6-hydroxy-7,8-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutane]-5-carbaldehyde as a yellow solid. 1H-NMR (300 MHz, CDCl3) δ=1.65-1-70 (m, 1H), 1.80-1.97 (m, 2H), 2.06-2.27 (m, 11H), 3.06-3.11 (t, 2H), 10.20 (s, 1H), 12.13 (s, 1H) ppm. MS (m/z)=247 (M+H+).

Workup

customThe solution was flushed with Argon
temperaturewarmed to room temperature
stirringstirred overnight
washthe solution was washed with water
dry with materialdried over Na2SO4
customThe crude material was purified on a silica column
washeluting with 1:8 EtOAc/hexane

Sources & evidence

ORD record: ord-620e3c4efc4740908816f9a7ab6f8154
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07576094B2

Reaction notes

Loading…