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alpha-Chlorohydrin, (+)- → (S)-3-{4-[5-(2-Cyclopentyl-6-methoxy-pyridin-4-yl)-[1,3,4]oxadiazol-2-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diol

HRID 245124
Notes
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Reaction equation

HRID 245124 reaction equation
[CH:1]1([C:6]2[CH:11]=[C:10]([C:12]3[O:16][C:15]([C:17]4[CH:22]=[C:21]([CH3:23])[C:20]([OH:24])=[C:19]([CH2:25][CH3:26])[CH:18]=4)=[N:14][N:13]=3)[CH:9]=[C:8]([O:27][CH3:28])[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[CH2:30][C@@H:31]([OH:34])[CH2:32][OH:33]>C(O)(C)C.[OH-].[Na+].CC(=O)OCC>[CH:1]1([C:6]2[CH:11]=[C:10]([C:12]3[O:16][C:15]([C:17]4[CH:22]=[C:21]([CH3:23])[C:20]([O:24][CH2:30][C@@H:31]([OH:34])[CH2:32][OH:33])=[C:19]([CH2:25][CH3:26])[CH:18]=4)=[N:14][N:13]=3)[CH:9]=[C:8]([O:27][CH3:28])[N:7]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 2

HCID 148904alpha-Chlorohydrin, (+)-HCID 1363910184-[5-(2-Cyclopentyl-6-methoxy-pyridin-4-yl)-[1,3,4]oxadiazol-2-yl]-2-ethyl-6-methyl-phenol

Product 1

HCID 49872363(S)-3-{4-[5-(2-Cyclopentyl-6-methoxy-pyridin-4-yl)-[1,3,4]oxadiazol-2-yl]-2-ethyl-6-methyl-phenoxy}-propane-1,2-diolYield 71.8%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolvent
HCID 8857
Ethyl Acetate
Solvent
HCID 14798Sodium HydroxideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,3,4]oxadiazol-2-yl]-2-ethyl-6-methyl-phenol (100 mg, 264 μmol) and (S)-3-chloro-propane-1,2-diol (244 mg, 2.64 mmol) in isopropanol (4 mL) and 3 N aq. NaOH (1 mL) is stirred at 70° C. for 48 h. The mixture is diluted with EA (50 mL), washed with 1 M aq. NaOH solution (20 mL) followed by brine (20 mL), dried over MgSO4, filtered and concentrated. The crude product is purified by prep. HPLC to give the title compound (86 mg) as a white solid; LC-MS**: tR=0.83 min, [M+H]+=454.12; 1H NMR (CDCl3): δ1.33 (t, J=7.5 Hz, 3H), 1.65-1.80 (m, 2H), 1.83-1.96 (m, 4H), 2.05-2.15 (m, 2H), 2.42 (s, 3H), 2.78 (q, J=7.3 Hz, 2H), 3.19-3.30 (m, 1H), 3.82-3.99 (m, 4H), 4.02 (s, 3H), 4.15-4.23 (m, 1H), 7.22 (s, 1H), 7.48 (s, 1H), 7.84 (s, 1H), 7.86 (s, 1H).

Workup

  1. washwashed with 1 M aq. NaOH solution (20 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product is purified by prep

Sources & evidence

ORD record
ord-793b7cd879334be39a2eb44e21297400
Source dataset
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08658675B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes