alpha-Chlorohydrin, (+)- → HCID 23729209, compound

HRID 1676131Notes

Reaction equation

HRID 1676131 reaction equation
[OH:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([CH2:9][CH2:10][C:11]([C:13]2[S:14][CH:15]=[C:16]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:17]=2[CH2:18][CH2:19][CH3:20])=[O:12])=[CH:4][C:3]=1[CH3:25].Cl[CH2:27][C@@H:28]([OH:31])[CH2:29][OH:30]>C(O)(C)C.[OH-].[Na+].O>[OH:31][C@@H:28]([CH2:29][OH:30])[CH2:27][O:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([CH2:9][CH2:10][C:11]([C:13]2[S:14][CH:15]=[C:16]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:17]=2[CH2:18][CH2:19][CH3:20])=[O:12])=[CH:4][C:3]=1[CH3:25]

Participants

6

Reactant 2

HCID 148904alpha-Chlorohydrin, (+)-2×HCID 59497865HCID 59497865, compound

Product 1

HCID 23729209HCID 23729209, compoundYield 13.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 3-(4-hydroxy-3,5-dimethyl-phenyl)-1-(4-isobutyl-3-propyl-thiophen-2-yl)-propan-1-one (108 mg, 0.301 mmol) in isopropanol (5 mL), 3 N aq. NaOH (3 mL) followed by (S)-3-chloro-1,2-propanediol (167 mg, 1.51 mmol) is added. The mixture is stirred at 70° C. for 4 h. After 4, 5, 6, 7 and 8 h an additional portion of (S)-3-chloro-1,2-propanediol (5×97 mg, 0.878 mmol) is added. After the last addition, stirring is continued at 60° C. for 16 h. The mixture is diluted with water and extracted with diethyl ether. The organic extract is dried over MgSO4, filtered and evaporated. The crude product is purified by prep. HPLC to give 3-[4-((S)-2,3-dihydroxy-propoxy)-3,5-dimethyl-phenyl]-1-(4-isobutyl-3-propyl-thiophen-2-yl)-propan-1-one (18 mg) as an almost colourless resin; LC-MS: tR=1.09 min, [M+1]=433.40; 1H NMR (CDCl3): δ 7.08 (s, 1H), 6.87 (s, 2H), 4.11-4.03 (m, 1H), 3.90-3.70 (m, 4H), 3.14-3.06 (m, 2H), 2.94-2.82 (m, 4H), 2.60 (s br, 2H), 2.40 (d, J=7.0 Hz, 2H), 2.24 8s, 6H), 1.90-1.78 (m, 1H), 1.56-1.46 (m, 2H), 1.00 8t, J=7.0 Hz, 3H), 0.93 (d, J=6.4 Hz, 6H).

Workup

  1. additionis added
  2. additionAfter the last addition
  3. stirringstirring
  4. waitis continued at 60° C. for 16 h
  5. extractionextracted with diethyl ether
  6. extractionThe organic extract
  7. dry with materialis dried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude product is purified by prep

Sources & evidence

ORD record
ord-558bcad08965423d8b1b4db4e4f89e63
Source dataset
uspto-grants-2011_08
Patent number
US08003800B2

Reaction notes

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