Allyl bromide → HCID 19874769, compound

HRID 465630Notes

Reaction equation

HRID 465630 reaction equation
C(N[CH:5]([CH3:7])[CH3:6])(C)C.C([Li])CCC.[CH2:13]([O:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][C:26]([O:28][CH2:29][CH2:30][CH2:31][O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:27])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(Br)C=C>O1CCCC1.CCCCCC.CN(C)P(N(C)C)(N(C)C)=O>[CH2:13]([O:20][CH2:21][CH2:22][CH2:23][O:24][CH:25]([CH2:7][CH:5]=[CH2:6])[C:26]([O:28][CH2:29][CH2:30][CH2:31][O:32][CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)=[O:27])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 7841Allyl bromideHCID 7912DiisopropylamineHCID 19874747HCID 19874747, compoundHCID 178418339Butyllithium

Product 1

HCID 19874769HCID 19874769, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of diisopropylamine (0.075 ml, 0.53 mmol) in dry tetrahydrofuran (0.5 ml) is cooled to 0° C. and a 2.5M solution of n-butyllithium in hexane is added (0.19 ml, 0.47 mmol). The solution is stirred at 0° C. for 15 minutes and then cooled down to -78° C. A solution of 3-benzyloxypropyl 2-[(3-benzyloxypropyl)oxy]acetate (0.165 g 0.44 mmol) in tetrahydrofuran (1 ml) is added slowly. The mixture is allowed to stir at -78° for 1 hour and then hexamethyl phosphoramide (0.5 ml) is added, followed by allyl bromide (0.23 ml, 2.7 mmol). The mixture is allowed to warm to room temperature over 3 hours and then quenched using saturated aqueous ammonium chloride. The mixture is extracted with ether (3×15 ml) and the combined organic extracts are washed with water (3×45 ml) and brine (30 ml). The organic layer is dried, evaporated and the residue purified by flash chromatography on silica gel using ethyl acetate/hexane (1:4) as eluent to obtain 3-benzyloxypropyl 2-[(3-benzyloxypropyl)oxy]pent-4-enoate. IR (CH2Cl2): 1745, 1644, 1195, 1101 cm-1. Reduction of the ester with diisobutyl aluminum hydride, followed by conversion of the alcohol as previously described yields methyl 4-[(3-benzyloxypropyl)-oxy]-hept-6-enoate. This is in turn converted to methyl 4-[3-(N-t-butoxycarbonyl-p-chlorophenylsulfonamido)-propyloxy]-7-(3-pyridyl)-heptanoate as starting material for compound under (a), or methyl 4-[3-(N-t-butoxycarbonyl-p-chlorophenylsulfonamido)-propyloxy]-6-(3-pyridyloxy)-hexanoate for compound under (b), according to methods described in the previous examples.

Workup

  1. temperaturecooled down to -78° C
  2. stirringto stir at -78° for 1 hour
  3. temperatureto warm to room temperature over 3 hours
  4. customquenched
  5. extractionThe mixture is extracted with ether (3×15 ml)
  6. washthe combined organic extracts are washed with water (3×45 ml) and brine (30 ml)
  7. customThe organic layer is dried
  8. customevaporated
  9. customthe residue purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-deb53aa81d2c4bd692b7bb852c369a19
Source dataset
uspto-grants-1992_10
Patent number
US05153214

Reaction notes

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