Hydrochloric Acid → trans 1-(t-Butyldimethylsilyl)-3-phenylacetyl-4-tritylthio-2-azetidinone

HRID 1680358Notes

Reaction equation

HRID 1680358 reaction equation
[Si:1]([N:8]1[CH:11]([S:12][C:13]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:10][C:9]1=[O:32])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li+].CC([N-]C(C)C)C.[Li]CCCC.C(NC(C)C)(C)C.[C:53]1([CH2:59][C:60](OCC)=[O:61])[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1.Cl>C1COCC1.CCOCC>[Si:1]([N:8]1[C@@H:11]([S:12][C:13]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C@H:10]([C:60](=[O:61])[CH2:59][C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[C:9]1=[O:32])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 7590Ethyl phenylacetateHCID 7912DiisopropylamineHCID 2724682Lithium diisopropylamideHCID 129287451-t-Butyldimethylsilyl-4-tritylthio-2-azetidinoneHCID 178418339Butyllithium

Product 1

HCID 86737797trans 1-(t-Butyldimethylsilyl)-3-phenylacetyl-4-tritylthio-2-azetidinoneYield 79.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

1-t-Butyldimethylsilyl-4-tritylthio-2-azetidinone (18.32 g, 40 mmol) in dry THF (100 ml) was added dropwise under N2 to a cooled (-78° C.) LDA solution [prepared under N2, at -78° C. from dropwise addition of 1.6 M n-BuLi (101.25 ml, 162 mmol) to diisopropyl amine (22.95 ml, 162 mmol) in dry THF (150 ml) and stirred at -78° C. for 30 min]. The mixture was stirred at -78° C. for 30 min and ethyl phenylacetate (15.66 g, 15.12 ml 15.12 ml, 93.6 mmol) in dry THF (50 ml) was added and the reaction mixture was stirred at -78° C. for 2 h. It was poured onto ice-1 N HCl (pH 5-6) and extracted with ether several times. The ether solution was washed with brine and dried (Na2SO4 ). It was evaporated to dryness to give 33.7 g of a crude solid. This was dissolved in ether (10 ml) and triturated with pentane (200 ml). The solid was filtered and washed several times with pentane to give 18.3 g of a white solid (79.6%) mp 141-143. 1Hmr (CDCl3 δ: 7.0-7.6 (20H, m), 4.8 (H, d), 3.7 (H, d), 3.53 (H, s), 3.43 (H, s) 1.5 (9H, s) and 0.3 ppm (6H, s).

Workup

  1. stirringThe mixture was stirred at -78° C. for 30 min
  2. stirringthe reaction mixture was stirred at -78° C. for 2 h
  3. extractionextracted with ether several times
  4. washThe ether solution was washed with brine
  5. dry with materialdried (Na2SO4 )
  6. customIt was evaporated to dryness
  7. customto give 33.7 g of a crude solid
  8. customtriturated with pentane (200 ml)
  9. filtrationThe solid was filtered
  10. washwashed several times with pentane

Sources & evidence

ORD record
ord-105d029834e8495c9de938098d1f18ca
Source dataset
uspto-grants-1981_06
Patent number
US04272437

Reaction notes

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