2,6-Lutidine → HCID 54513149, compound

HRID 975681Notes

Reaction equation

HRID 975681 reaction equation
S(Cl)([Cl:3])=O.N1C(C)=CC=CC=1C.[CH2:13]([O:16][C:17]([N:19]1[CH2:23][C@H:22]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[CH2:21][C@H:20]1[CH:32]([C:34]1[CH:35]=[N:36][CH:37]=[N:38][CH:39]=1)O)=[O:18])[CH:14]=[CH2:15].[OH-].[Na+]>ClCCl>[CH2:13]([O:16][C:17]([N:19]1[CH2:23][C@H:22]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[CH2:21][C@H:20]1[CH:32]([C:34]1[CH:35]=[N:36][CH:37]=[N:38][CH:39]=1)[Cl:3])=[O:18])[CH:14]=[CH2:15]

Participants

6

Reactant 4

HCID 79372,6-Lutidine3×HCID 14798Sodium HydroxideHCID 24386Thionyl Chloride3×HCID 57282382HCID 57282382, compound

Product 1

HCID 54513149HCID 54513149, compoundYield 47.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of thionyl chloride (6.05 g) in dichloromethane (70 ml) was added 2,6-lutidine (6.53 g) at 5° C. to 10° C. After the solution was stirred for 30 minutes at the same temperature, the solution of 1-{(2S,4R)-1-allyloxycarbonyl-4-(t-butyldimethylsilyloxy)-pyrrolidin-2-yl}-1-(pyrimidin-5-yl)methanol (20.0 g) in dichloromethane (100 ml) was slowly dropped thereto below 10° C. After the reaction mixture was stirred for an hour below 10° C., it was stirred at room temperature for 2 hours, then thionyl chloride (6.05 g) and 2,6-lutidine (6.53 g) were added to the reaction mixture. After the reaction mixture was stirred another one hour, thionyl chloride (6.05 g) and 2,6-lutidine (6.53 g) were added to the reaction mixture. The reaction mixture was stirred at room temperature for 2 hours, then it was poured into ice-water (500 ml) and dichloromethane (400 ml) and adjusted to pH 5.1 with saturated aqueous sodium hydroxide below 15° C. The organic layer was separated and washed with water (400 ml) at pH 4.3 and brine (350 ml). The organic layer was dried over magnesiumsulfate and evaporated. The residue was subjected to column chromatography on silica gel (200 g) [solvent; hexane:ethyl acetate=5:1 to 2:1 to 1:1] to give 1-{(2S,4R)-1-allyloxycarbonyl-4-(t-butyldimethylsilyloxy)-pyrrolidin-2-yl }-1-(pyrimidin-5-yl)-1-chloromethane (9.9 g) as an oil.

Workup

  1. custombelow 10° C
  2. stirringAfter the reaction mixture was stirred for an hour below 10° C.
  3. stirringit was stirred at room temperature for 2 hours
  4. stirringAfter the reaction mixture was stirred another one hour
  5. stirringThe reaction mixture was stirred at room temperature for 2 hours
  6. customThe organic layer was separated
  7. washwashed with water (400 ml) at pH 4.3 and brine (350 ml)
  8. dry with materialThe organic layer was dried over magnesiumsulfate
  9. customevaporated

Sources & evidence

ORD record
ord-297ad9021c1e4a89a2030cd86ebf2e9a
Source dataset
uspto-grants-1997_03
Patent number
US05608056

Reaction notes

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