2-Aminophenol → HCID 45086957, compound

HRID 2267620Notes

Reaction equation

HRID 2267620 reaction equation
[C:1]1([C@@H:7]2[O:9][C@H:8]2[C:10]([O-:12])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[K+].ClC(OCC(C)C)=O.CN1CCOCC1.[NH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[OH:36]>C1COCC1>[OH:36][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=1[NH:29][C:10]([C@H:8]1[C@H:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[O:9]1)=[O:12]

Participants

6

Reactant 4

HCID 58012-AminophenolHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 23702683HCID 23702683, compound

Product 1

HCID 45086957HCID 45086957, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

To a stirred suspension of potassium (2R,3S)-3-phenyloxirane-2-carboxylate (64a) (4.040 g, 20.00 mmol) in dry THF (100 mL) under nitrogen cooled in an ice-water bath was added isobutyl chloroformate (2.730 g, 20.00 mmol) slowly via syringe. NMM (0.460 mg, 4.55 mmol) was added and the mixture stirred while gradually warming to 10° C. over 75 min. The mixture was cooled to 0° C. and 2-aminophenol was added, then the cooling bath was removed and the reaction stirred at ambient temperature for 24 h. The reaction was diluted with diethyl ether (100 mL) then filtered through diatomaceous earth to remove suspended solids. Rotary evaporation of the solution afforded a yellow solid that was triturated with diethyl ether and collected by filtration. The solid was rinsed on the filter with additional diethyl ether to afford pure title compound (3.920 g, 77%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ4.00 (d, 1H, J=1.8 Hz), 4.22 (d, 1H, J=1.8 Hz), 6.80 (m, 1H), 6.87-7.00 (m, 2H), 7.40 (s, 5H), 7.95 (d, 1H, J=7.9 Hz), 9.27 (s, 1H), 9.97 (s, 1H). 13C-DEPT NMR (75 MHz, DMSO-d6) δ57.7 (CH), 58.4 (CH), 115.5 (CH), 119.4 (CH), 121.6 (CH), 125.1 (CH), 125.8 (C), 126.5 (CH), 128.9 (CH), 129.1 (CH), 135.9 (C), 147.7 (C), 165.4 (C). MS APCI, m/z=256 (M+1). LC/MS: 2.12 min.

Workup

  1. temperaturecooled in an ice-water bath
  2. temperatureThe mixture was cooled to 0° C.
  3. customthe cooling bath was removed
  4. stirringthe reaction stirred at ambient temperature for 24 h
  5. additionThe reaction was diluted with diethyl ether (100 mL)
  6. filtrationthen filtered through diatomaceous earth
  7. customto remove
  8. customRotary evaporation of the solution
  9. customafforded a yellow solid
  10. customthat was triturated with diethyl ether
  11. filtrationcollected by filtration
  12. washThe solid was rinsed on the
  13. filtrationfilter with additional diethyl ether

Sources & evidence

ORD record
ord-6b1ab03add604eba8f75ee0193da0d19
Source dataset
uspto-grants-2010_12
Patent number
US07858776B2

Reaction notes

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