Hydrochloric Acid → HCID 57282382, compound

HRID 975680Notes

Reaction equation

HRID 975680 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1.C([Li])CCC.[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]=[O:33])=[O:18])[CH:14]=[CH2:15].Cl>O1CCCC1.C(OCC)C.CCCCCC.C(OCC)(=O)C.O>[CH2:13]([O:16][C:17]([N:19]1[CH2:23][C@H:22]([O:24][Si:25]([C:28]([CH3:30])([CH3:29])[CH3:31])([CH3:26])[CH3:27])[CH2:21][C@H:20]1[CH:32]([C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1)[OH:33])=[O:18])[CH:14]=[CH2:15]

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 783445-BromopyrimidineHCID 22870383(2S,4R)-1-allyloxycarbonyl-4-t-butyldimethylsilyloxy-2-formylpyrrolidineHCID 178418339Butyllithium

Product 1

HCID 57282382HCID 57282382, compoundYield 66.6%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under nitrogen atmosphere to a solution of 5-bromopyrimidine (18.3 g) in tetrahydrofuran (360 ml) and diethyl ether (360 ml) was slowly dropped 1.56 mol/l n-butyllithium in hexane solution (73.6 ml) at -90° C. to -95° C. The reaction mixture was stirred at the same temperature for an hour, and then the solution of (2S,4R)-1-allyloxycarbonyl-4-(t-butyldimethylsilyloxy)-2-formylpyrrolidine (30.0 g) in tetrahydrofuran (60 ml) and ether (60 ml) was dropped into the reaction mixture below -85° C. The reaction mixture was stirred at -50° C. for an hour, then water (150 ml) was dropped thereto below -10° C. The reaction mixture was poured into ethyl acetate (500 ml) and ice-water (300 ml) and adjusted to pH 7.0 with concentrated hydrochloric acid. Insoluble material was removed by filtration and washed with ethyl acetate (200 ml). The organic layer was separated, washed with water (300 ml) and brine (300 ml), and then dried over magnesium sulfate, and evaporated. The residue was subjected to column chromatography on silica gel (360 g) [solvent; hexane:ethyl acetate=4:1 to 2:1 to 1:3] to give 1-{(2S,4R)-1-allyloxycarbonyl-4-(t-butyldimethyl-silyloxy) pyrrolidin-2-yl}-1-(pyrimidin-5-yl)methanol (25.1 g) as an oil.

Workup

  1. customat -90° C. to -95° C
  2. stirringThe reaction mixture was stirred at -50° C. for an hour
  3. custombelow -10° C
  4. customInsoluble material was removed by filtration
  5. washwashed with ethyl acetate (200 ml)
  6. customThe organic layer was separated
  7. washwashed with water (300 ml) and brine (300 ml)
  8. dry with materialdried over magnesium sulfate
  9. customevaporated

Sources & evidence

ORD record
ord-72ff7db4c3104f06aa103588bd22c134
Source dataset
uspto-grants-1997_03
Patent number
US05608056

Reaction notes

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