(-)-Epichlorohydrin → 2-Chloro-5-[(2S)-3-chloro-2-hydroxypropyl]-N-[(4-methoxyphenyl)methyl]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)benzamide

HRID 1765543Notes

Reaction equation

HRID 1765543 reaction equation
C([Mg]Cl)(C)C.[Cl:6][C:7]1[CH:35]=[CH:34][C:33](I)=[CH:32][C:8]=1[C:9]([N:11]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=1)[CH2:12][C:13]12[CH2:22][CH:17]3[CH2:18][CH:19]([CH2:21][CH:15]([CH2:16]3)[CH2:14]1)[CH2:20]2)=[O:10].[CH2:37]([C@@H:39]1[O:41][CH2:40]1)[Cl:38]>O1CCCC1.C(=O)(O)[O-].[Na+].O>[Cl:6][C:7]1[CH:35]=[CH:34][C:33]([CH2:40][C@H:39]([OH:41])[CH2:37][Cl:38])=[CH:32][C:8]=1[C:9]([N:11]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=1)[CH2:12][C:13]12[CH2:22][CH:17]3[CH2:18][CH:19]([CH2:21][CH:15]([CH2:16]3)[CH2:14]1)[CH2:20]2)=[O:10]

Participants

7

Reactant 3

HCID 2734062(-)-EpichlorohydrinHCID 211074122-Chloro-5-iodo-N-[(4-methoxyphenyl)methyl]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)benzamideHCID 178418918HCID 178418918, compound

Product 1

HCID 211074072-Chloro-5-[(2S)-3-chloro-2-hydroxypropyl]-N-[(4-methoxyphenyl)methyl]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)benzamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
30 °C

Procedure

iso-Propylmagnesium chloride solution (2M in tetrahydrofuran, 72.9 mL) was added to a stirred solution of 2-chloro-5-iodo-N-[(4-methoxyphenyl)methyl]-N-(tricyclo [3.3.1.13,7]dec-1-ylmethyl)benzamide (Example 15a) (72.87 g) in anhydrous tetrahydrofuran (1 L) at 0° C. under nitrogen. After 30 minutes, copper(I) bromide dimethylsulphide complex (0.68 g) followed by (R)-(−)epichlorohydrin (11.4 mL) were added. The mixture was warmed to 30° C. for 2 hours then diluted with saturated sodium bicarbonate solution (1 L) and water (500 mL) then extracted with ethyl acetate (2×1 L). Organic extracts were dried over anhydrous magnesium sulphate, filtered and evaporated under reduced pressure. The residual oil was dissolved in methanol (600 mL), stirred overnight and the precipitated solid filtered and dried in vacuo to give the titled compound (52.25 g).

Workup

  1. additionwere added
  2. extractionthen extracted with ethyl acetate (2×1 L)
  3. dry with materialOrganic extracts were dried over anhydrous magnesium sulphate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. dissolutionThe residual oil was dissolved in methanol (600 mL)
  7. filtrationthe precipitated solid filtered
  8. customdried in vacuo

Sources & evidence

ORD record
ord-bb451aa354b94ec9a26569d396d3548b
Source dataset
uspto-grants-2007_06
Patent number
US07227038B2

Reaction notes

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