Ethylene Oxide → tert-butyl N-[2-(2-hydroxyethyl)-3-methoxyphenyl]carbamate

HRID 1374945Notes

Reaction equation

HRID 1374945 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:16]=[CH:15][C:12]([O:13]C)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:17]([Li])(C)(C)C.[CH2:22]1[O:24][CH2:23]1.[Cl-].[NH4+]>CCOCC>[OH:13][CH2:12][CH2:15][C:16]1[C:23]([O:24][CH3:22])=[CH:17][CH:11]=[CH:10][C:9]=1[NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7]

Participants

6

Reactant 4

HCID 6354Ethylene OxideHCID 25517Ammonium ChlorideHCID 2741326tert-Butyl-4-methoxycarbanilateHCID 178418306HCID 178418306, compound

Product 1

HCID 22282726tert-butyl N-[2-(2-hydroxyethyl)-3-methoxyphenyl]carbamateYield 37%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-20 °C

Procedure

A stirred solution of N-tert-butoxycarbonyl-anisidine (431 g, 1.93 mol) in ether (2 L) under an argon atmosphere was cooled to −20° C. A solution of tert-butyllithium (1.7 M, hexanes, 2.5 L, 4.25 mol) was added dropwise and the reaction was stirred for 3 h at −20° C. The reaction was cooled to −50° C. and ethylene oxide (136 g, 3.09 mol) was added dropwise. The reaction was warmed to 0° C. over 1 h and then stirred at room temperature for 1 h. The reaction was poured onto saturated aqueous ammonium chloride solution (2.5 L) and the mixture was extracted with ether (3×2.5 L). The organic extracts were combined and concentrated in vacuo to afford a pale yellow oil which was purified by column chromatography [SiO2; heptane-ethyl acetate (5:1)] to afford the title compound (176 g, 37%) as a yellow crystalline solid; NMR (400 MHz, CDCl3) δH 1.51 (9H, br s), 2.91 (2H, t, J 6.0 Hz), 3.79 (3H, s), 3.87 (2H, q, J 5.0 Hz, 10.5 Hz), 6.64 (1H, d, J 8.0 Hz), 7.18 (1H, t, J 9.0 Hz), 7.38 (1H, m), 7.55 (1H, br s); IR νmax (Nujol)/cm−1 3407, 3212, 2955, 2854, 1721, 1592, 1508, 1476, 1438, 1370, 1267, 1234, 1162, 1047 and 773.

Workup

  1. temperatureThe reaction was cooled to −50° C.
  2. temperatureThe reaction was warmed to 0° C. over 1 h
  3. stirringstirred at room temperature for 1 h
  4. extractionthe mixture was extracted with ether (3×2.5 L)
  5. concentrationconcentrated in vacuo
  6. customto afford a pale yellow oil which
  7. customwas purified by column chromatography [SiO2; heptane-ethyl acetate (5:1)]

Sources & evidence

ORD record
ord-300b089b30364bc190a84c4f5dd043e7
Source dataset
uspto-grants-2007_01
Patent number
US07166632B2

Reaction notes

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