Acetyl chloride → HCID 22633624, compound

HRID 2417143Notes

Reaction equation

HRID 2417143 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:22](Cl)(=[O:24])[CH3:23]>C(Cl)Cl>[C:22]([O:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:9][CH2:10][C:11](=[O:14])[CH2:12][CH2:13]2)=[CH:6][CH:7]=1)(=[O:24])[CH3:23]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 45989164-(4'-Hydroxyphenyl)cyclohexanone

Product 1

HCID 22633624HCID 22633624, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Step 1. To a mixture of 4-(4-hydroxyphenyl)cyclohexanone (19.0 g, 0.1 mol) and triethylamine (40.4 g, 0.4 mol) in CH2Cl2 (700 ml) at 0° C. was added dropwise acetyl chloride (15.7 g, 0.2 mol). After the addition was finished, the reaction mixture was warmed to rt and stirred overnight. The reaction mixture was washed with water and brine, dried over MgSO4, and concentrated. The crude product was crystallized from 95% aq. ethanol to afford 4-(4-acetoxyphenyl)-cyclohexanone (17.6 g, 76%) as a colorless solid. mp 104-106° C. (95% aq. ethanol); 1H NMR (500 MHz, CDCl3) δ 1.88-1.98 (m, 2H), 2.20-2.26 (m, 2H), 2.48-2.54 (m, 4H), 2.30 (s, 3H), 3.00-3.07 (m, 1H), 7.03 (d, J=8.7 Hz, 2H), 7.25 (d, J=8.7 Hz, 2H). Step 2. A solution of O-methyl 2-adamantanone oxime (16.0 g, 89 mmol) and 4-(4-acetoxyphenyl)cyclohexanone (13.8 g, 59 mmol) in cyclohexane (400 ml) and CH2Cl2 (100 ml) was treated with ozone according to the general procedure. The crude product was triturated with ethanol (200 ml) to afford adamantane-2-spiro-3′-8′-(4′-acetoxyphenyl)-1′,2′,4′-trioxaspiro[4.5]decane (16.4 g, 70%) as a colorless solid. mp 149-151° C. (ethanol); 1H NMR (500 MHz, CDCl3) δ 1.64-2.08 (m, 22H), 2.29 (s, 3H), 2.50-2.60 (m, 1H), 7.00 (d, J=8.2 Hz, 2H), 7.20 (d, J=8.2 Hz, 2H). Step 3. A mixture of adamantane-2-spiro-3′-8′-(4′-acetoxyphenyl)-1′,2′,4′-trioxaspiro[4.5]decane (16.4 g, 41 mmol) and 15% aq. KOH (65 ml) in THF/MeOH (1:2, 500 ml) was heated at 50° C. for 4 h. After being cooled to rt, the reaction mixture was concentrated to 70 ml, diluted with water (70 ml), and acidified with acetic acid (30 ml). The precipitate was collected by filtration to afford trioxolane OZ288 (14.36 g, 98%) as a colorless solid. mp 136-138° C.; 1H NMR (500 MHz, CDCl3) δ 1.56-2.18 (m, 22H), 2.41-2.58 (m, 1H), 5.90 (br s, 1H), 6.76 (d, J=8.5 Hz , 2H), 7.05 (d, J=8.5 Hz, 2H); 13C NMR (125.7 MHz, CDCl3) δ 26.49, 26.89, 31.65, 34.75, 34.80, 36.41, 36.81, 42.05, 108.46, 111.35, 115.22, 127.71, 138.03, 154.26. Anal. Calcd for C22H28O4: C, 74.13; H, 7.92. Found: C, 73.90; H, 7.85.

Workup

  1. additionAfter the addition
  2. washThe reaction mixture was washed with water and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe crude product was crystallized from 95% aq. ethanol

Sources & evidence

ORD record
ord-95863f1fd2714cf0ba479488c170705b
Source dataset
uspto-grants-2004_11
Patent number
US06825230B2

Reaction notes

Loading…