Hydrochloric Acid → tert-butyl N-((1S)-3-oxocyclopentyl)carbamate

HRID 1420302Notes

Reaction equation

HRID 1420302 reaction equation
C([Li])CCC.C[Si](C)(C)N[Si](C)(C)C.C1(COC(=O)[CH2:24][CH2:25][C@H:26]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:27][C:28]([O:30]C)=O)C=CC=CC=1.Cl.[H][H]>CCCCCC.O1CCCC1.ClCCl.C(O)C.[Pd]>[CH3:39][C:36]([O:35][C:33](=[O:34])[NH:32][C@H:26]1[CH2:25][CH2:24][C:28](=[O:30])[CH2:27]1)([CH3:37])[CH3:38]

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 13838HexamethyldisilazaneHCID 54122426(S)-3-[[(1,1-Dimethylethoxy)carbonyl]amino]-hexanedioic acid 1-methyl 6-(phenylmethyl) esterHCID 178418339ButyllithiumHCID 178418361HCID 178418361, compound

Product 1

HCID 45091924tert-butyl N-((1S)-3-oxocyclopentyl)carbamateYield 52.7%

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-60 °C

Procedure

2.5M n-Butyllithium in hexane (5.83 ml) was added dropwise to a stirred solution of 1,1,1,3,3,3-hexamethyldisilazane (3.16 ml, 15 mmol) in tetrahydrofuran (30 ml) at 4° C. After 20 min the solution was cooled to -60° C. and (S)-3-[[(1,1-dimethylethoxy)carbonyl]amino]-hexanedioic acid 1-methyl 6-(phenylmethyl) ester (1.522 g, 4.16 mmol) in tetrahydrofuran (10 ml) was added dropwise over 5 min. The solution was stirred for 10 min before the addition of pH7 buffer (5 ml) and the mixture was then diluted with dichloromethane (200 ml) and pH7 buffer (300 ml). The aqueous phase was adjusted to pH6.5 with 2M hydrochloric acid and then the organic phase was separated. The aqueous phase was extracted with dichloromethane (2×200 ml) and the combined organic phase was dried (MgSO4) then evaporated to leave a solid. The solid was dissolved in ethanol (45 ml) and hydrogenated over 10% palladium-on-carbon (0.5 g) for 4 h. The hydrogen was replaced by nitrogen and the reaction was stirred for a further 18 h then filtered through celite and the pad was washed with ethanol. The filtrate and washings were combined and evaporated to leave a solid which was purified by column chromatography on flash silica eluting with 25-40% ethyl acetate in cyclohexane to give the title compound (0.437 g) as a white solid which crystallised from isopropyl ether, m.p. 97°-98° C., [α]D -48° (CHCl3 c=0.52%).

Workup

  1. customthe organic phase was separated
  2. extractionThe aqueous phase was extracted with dichloromethane (2×200 ml)
  3. dry with materialthe combined organic phase was dried (MgSO4)
  4. customthen evaporated
  5. customto leave a solid
  6. stirringthe reaction was stirred for a further 18 h
  7. filtrationthen filtered through celite
  8. washthe pad was washed with ethanol
  9. customevaporated
  10. customto leave a solid which
  11. customwas purified by column chromatography on flash silica eluting with 25-40% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-17beea3d81d1439891f606e9ce336770
Source dataset
uspto-grants-1999_03
Patent number
US05889178

Reaction notes

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