Diisopropylamine → (3S,4R)-1-(t-butyldimethylsilyl)-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-4-(3-benzyloxycarbonyl-2-hydroxypropyl)-azetidin-2-one

HRID 435086Notes

Reaction equation

HRID 435086 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[C:13]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)(=[O:15])[CH3:14].[Si:24]([N:31]1[C@H:34]([CH2:35][CH:36]=[O:37])[C@@H:33]([C@H:38]([O:40][Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42])[CH3:39])[C:32]1=[O:48])([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25]>O1CCCC1>[Si:24]([N:31]1[C@H:34]([CH2:35][CH:36]([OH:37])[CH2:14][C:13]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[C@@H:33]([C@H:38]([O:40][Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:42])[CH3:43])[CH3:39])[C:32]1=[O:48])([C:27]([CH3:30])([CH3:28])[CH3:29])([CH3:26])[CH3:25]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 8785Benzyl acetateHCID 11003560(3S,4R)-1-(t-butyldimethylsilyl)-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-4-(2-oxoethyl)azetidin-2-oneHCID 178418339Butyllithium

Product 1

HCID 13104634(3S,4R)-1-(t-butyldimethylsilyl)-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-4-(3-benzyloxycarbonyl-2-hydroxypropyl)-azetidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium (1.81 mmol) is added by syringe to a solution of diisopropylamine (1.81 mmol) in 9 ml of freshly distilled tetrahydrofuran at -78° C. The resulting solution is stirred for 15 min at -78° C. Benzyl acetate (1.81 mmol) is then added dropwise by syringe and the resulting solution is stirred at -78° C. for 20 min. A solution of (3S,4R)-1-(t-butyldimethylsilyl)-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-4-(2-oxoethyl)azetidin-2-one (1.64 mmol) in 3 ml of anhydrous tetrahydrofuran is added slowly by syringe. The reaction mixture is stirred at -78° C. an additional 15 min and then quenched by addition of saturated aqueous ammonium chloride solution. Ethyl acetate (50 ml) is added and the organic phase is separated, washed with water (2×10 ml) and brine and dried over magnesium sulfate. Removal of solvents in vacuo gives a white solid which is chromatographed on a short silica gel column (40 % ether in petroleum ether) to yield (3S,4R)-1-(t-butyldimethylsilyl)-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-4-(3-benzyloxycarbonyl-2-hydroxypropyl)-azetidin-2-one. n.m.r. (CDCl3) δ7.32 (s,5), δ5.1 (s,2), δ4.0 (m,3), δ2.4-3.8 (m,4), δ2.0 (m,2), δ1.25 (overlapping d, 3), δ0.95 (s,9), δ0.9 (s,9), δ0.3 (s,6), δ0.18 (s,6).

Workup

  1. stirringthe resulting solution is stirred at -78° C. for 20 min
  2. stirringThe reaction mixture is stirred at -78° C. an additional 15 min
  3. customquenched by addition of saturated aqueous ammonium chloride solution
  4. additionEthyl acetate (50 ml) is added
  5. customthe organic phase is separated
  6. washwashed with water (2×10 ml) and brine
  7. dry with materialdried over magnesium sulfate
  8. customRemoval of solvents in vacuo
  9. customgives a white solid which
  10. customis chromatographed on a short silica gel column (40 % ether in petroleum ether)

Sources & evidence

ORD record
ord-7f83744545a1426bbbf052fcd612c700
Source dataset
uspto-grants-1983_08
Patent number
US04400323

Reaction notes

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