Ethylene Glycol → N-(3-Methyl-5,7,8,9-tetrahydrospiro[benzo[7]annulene-6,2'-[1,3]dioxolan]-2-yl)acetamide

HRID 718814Notes

Reaction equation

HRID 718814 reaction equation
C1(C)C=CC=CC=1.[CH3:8][C:9]1[C:20]([NH:21][C:22](=[O:24])[CH3:23])=[CH:19][C:12]2[CH2:13][CH2:14][CH2:15][C:16](=[O:18])[CH2:17][C:11]=2[CH:10]=1.S(O)(C1C=CC(C)=CC=1)(=O)=O.[CH2:36](O)[CH2:37][OH:38]>CCOC(C)=O>[CH3:8][C:9]1[C:20]([NH:21][C:22](=[O:24])[CH3:23])=[CH:19][C:12]2[CH2:13][CH2:14][CH2:15][C:16]3([CH2:17][C:11]=2[CH:10]=1)[O:38][CH2:37][CH2:36][O:18]3

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 1140TolueneHCID 6101p-Toluenesulfonic acidHCID 86722423N-(3-Methyl-6-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)acetamide

Product 1

HCID 86722424N-(3-Methyl-5,7,8,9-tetrahydrospiro[benzo[7]annulene-6,2'-[1,3]dioxolan]-2-yl)acetamideYield 73%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

In a 50 L mechanically stirred vessel with Dean-Stark trap, toluene (22 L) was added to N-(3-methyl-6-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)acetamide (77) (1.04 kg, 4.50 mol). TosOH (84.0 g, 442 mmol) and ethylene glycol (750 mL, 13.4 mol) were added. The resulting mixture was heated to reflux overnight, cooled to rt, diluted with EtOAc (12 L) and washed with sat. aq. NaHCO3 (12 L) and sat. aq.s NaCl (12 L). The combined aq. washes were extracted with DCM (2×8 L). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel. The product containing fractions were combined and concentrated under reduced pressure to afford N-(3-methyl-5,7,8,9-tetrahydrospiro[benzo[7]annulene-6,2′-[1,3]dioxolan]-2-yl)acetamide (78) (900 g, 73% yield). 1H NMR (300 MHz, CDCl3): δ 7.45 (s, 1H), 7.03 (s, 1H), 6.92 (s, 1H), 3.96 (m, 4H), 3.02 (s, 2H), 2.76 (m, 2H), 2.20 (s, 3H), 2.18 (s, 3H), 1.98 (m, 2H), 1.74 (m, 2H).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux overnight
  3. washwashed with sat. aq. NaHCO3 (12 L) and sat. aq.s NaCl (12 L)
  4. extractionThe combined aq. washes were extracted with DCM (2×8 L)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified on silica gel
  9. additionThe product containing fractions
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ba2f2585a54e416ab34768429a49c9f7
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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