Formic Acid → HCID 19608274, compound

HRID 1602848Notes

Reaction equation

HRID 1602848 reaction equation
[OH:1][C:2]1[CH:13]=[C:12]2[O:14][CH2:15][O:16][C:11]2=[CH:10][C:3]=1[C:4]([NH:6][CH2:7][CH2:8][OH:9])=[O:5].[CH3:17]OC(OC)OC.C(O)=O>C(Cl)(Cl)Cl.C(OCC)(=O)C>[O:16]1[C:11]2[C:12](=[CH:13][C:2]3[O:1][CH:17]4[O:9][CH:8]=[CH:7][N:6]4[C:4](=[O:5])[C:3]=3[CH:10]=2)[O:14][CH2:15]1

Participants

6

Reactant 3

HCID 284Formic AcidHCID 9005Trimethyl orthoformateHCID 10977135HCID 10977135, compound

Product 1

HCID 19608274HCID 19608274, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(2-Hydroxy-4,5-methylenedioxybenzamido)ethanol (8.9 g; 40 mmol) was suspended in 320 mL dry chloroform, to which trimethylorthoformate (32 mL, 290 mmol) and formic acid (7.8 mL, 170 mmol) were added. The suspension was heated to reflux for 2.5 hours and diluted with ethyl acetate. The diluted solution was washed with a sodium bicarbonate buffer (pH 10), followed by a saturated sodium chloride solution and finally, dried over anhydrous sodium sulfate. The solution was evaporated onto silica gel and purified by multiple flash chromatographic steps on silica gel (ethyl acetate/hexane=1:1 or diethyl ether/hexane=9:1). Subsequent isolation of intermediate byproducts and treatment with formic acid yielded a total of 4.78 g (51%; after recrystallization from methylene chloride/diethyl ether) of (R,S)-7,8-dihydro-5aH, 10H-1,3-dioxolo[4,5-g]oxazolo[2,3-b][1,3]benzoxazin-10-one with mp=152-153° C. IR (thin film): 2899, 1667, 1460, 1420, 1260, 1117, 1034, and 926 cm-1. 1HNMR (500 MHz; CDCl3): δ 7.27 (1H, s), 6.53 (1H, s), 6.18 (1H, s), 6.015 (2H, AB quartet), 4.30 (1H, td, J=7 & 1.2 Hz), 4.22-4.28 (1H, m), 4.20 (1H, ddd, J=10, 7 & 1.4 Hz), and 3.55-3.60 ppm (1H, m.

Workup

  1. additionwere added
  2. temperatureThe suspension was heated
  3. temperatureto reflux for 2.5 hours
  4. washThe diluted solution was washed with a sodium bicarbonate buffer (pH 10)
  5. dry with materialfinally, dried over anhydrous sodium sulfate
  6. customThe solution was evaporated onto silica gel
  7. custompurified by multiple flash chromatographic steps on silica gel (ethyl acetate/hexane=1:1 or diethyl ether/hexane=9:1)

Sources & evidence

ORD record
ord-1018ae30bf59488ab1bcc5d5fd0ab41f
Source dataset
uspto-grants-1999_11
Patent number
US05985871

Reaction notes

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