Ethanolamine → HCID 11421728, compound

HRID 1825369Notes

Reaction equation

HRID 1825369 reaction equation
ClC(Cl)C.[CH:5]1([CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:16]([C:18]2[N:19]=[C:20]([C@@H:23]3[CH:28]4[O:29][C@@H:25]([CH2:26][CH2:27]4)[C@@H:24]3[CH2:30][C:31]3[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=3[CH2:38][CH2:39][C:40]([OH:42])=O)[O:21][CH:22]=2)=[O:17])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1.C(N(CC)CC)C.ClC(OCC)=O.[CH2:56]([CH2:58][NH2:59])[OH:57]>>[CH:5]1([CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:16]([C:18]2[N:19]=[C:20]([CH:23]3[CH:24]([CH2:30][C:31]4[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=4[CH2:38][CH2:39][C:40](=[O:42])[NH:59][CH2:58][CH2:56][OH:57])[CH:25]4[O:29][CH:28]3[CH2:27][CH2:26]4)[O:21][CH:22]=2)=[O:17])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]1

Participants

6

Reactant 5

HCID 700EthanolamineHCID 63651,1-DichloroethaneHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 23573773HCID 23573773, compound

Product 1

HCID 11421728HCID 11421728, compoundYield 37%

Procedure

A dichloroethane (0.3 mL) solution of 3-(2-{(1S,2R,3S)-3-[4-(4-Cyclohexyl-butylcarbamoy)-oxazol-2-yl]-7-oxa-bicyclo[2.2.1]hept-2-ylmethyl}-4fluoro-phenyl)-propionic acid (1) (30 mg, 0.057 mmol) was treated with triethylamine (12 μL, 0.086 mmol) and ethyl chloroformate (7 μL, 0.073 mmol). After 30 min., ethanolamine (10 μL, 0.17 mmol) was added and the solution stirred for 18 h. The resulting mixture was partitioned between 10 mL 1 M NaOH and 15 mL dichloromethane. The dichloromethane solution was washed with 1 M NaOH (6×10 mL). A small amount of brine was added to avoid an emulsion. The dichloromethane solution was then washed with brine (15 mL) and then was dried (Na2SO4), filtered and evaporated. Purification by preparative thin layer chromatography (4% methanol/dichloromethane) gave 12 mg (0.021 mmol, 37%) of the title compound. 1H NMR (300 MHz, ppm) δ 8.11 (s, 1 H) 7.3–7.2 (m, 1 H) 7.11–7.06 (m, 1 H) 6.84–6.78 (m, 2 H) 6.2–6.1 (m, 1 H) 5.00 (d, J=4.0 Hz, 1 H) 4.81 (d, J=4.4 Hz, 1 H) 3.7–3.6 (br m, 2 H) 3.5–3.3 (m, 6 H) 2.84–2.79 (m, 2 H) 2.66–2.57 (m, 1 H) 2.4–2.0 (m, 4 H) 1.9–0.8 (overlapping m, 21 H).

Workup

  1. customThe resulting mixture was partitioned between 10 mL 1 M NaOH and 15 mL dichloromethane
  2. washThe dichloromethane solution was washed with 1 M NaOH (6×10 mL)
  3. additionA small amount of brine was added
  4. washThe dichloromethane solution was then washed with brine (15 mL)
  5. dry with materialwas dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by preparative thin layer chromatography (4% methanol/dichloromethane)

Sources & evidence

ORD record
ord-ef7d63ce9dfd4f77b0d76f79fdf816be
Source dataset
uspto-grants-2006_05
Patent number
US07045634B2

Reaction notes

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