Ethylmorpholine → HCID 86755094, compound

HRID 850866Notes

Reaction equation

HRID 850866 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].S([O-])(O)(=O)=[O:8].[K+].[CH:13]1[C:25]2[CH:24]([CH2:26][O:27][C:28]([NH:30][C@H:31](C(O)=O)[CH2:32][CH:33]([CH3:35])[CH3:34])=[O:29])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]=2[CH:16]=[CH:15][CH:14]=1.[OH:39][C:40]1C2N=NNC=2C=CC=1.Cl.CN(C)[CH2:52][CH2:53][CH2:54]N=C=NCC.C([N:63]1[CH2:68][CH2:67][O:66][CH2:65][CH2:64]1)C>O1CCCC1.C(OCC)C.Cl.ClCCl>[CH:13]1[C:25]2[CH:24]([CH2:26][O:27][C:28]([NH:30][C@H:31]([C:68]([NH:63][C@H:64]([CH:65]([O:66][CH3:67])[O:39][CH3:40])[CH2:52][C:53]#[CH:54])=[O:8])[CH2:32][CH:33]([CH3:34])[CH3:35])=[O:29])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]=2[CH:16]=[CH:15][CH:14]=1

Participants

11

Reactant 6

HCID 7525EthylmorpholineHCID 516920Potassium bisulfateHCID 1549133Fmoc-leucineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21226445Aluminium lithium hydrideHCID 178418300HCID 178418300, compound

Product 1

HCID 86755094HCID 86755094, compound

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

10 ml (10 mmol) of 1M lithium aluminium hydride in tetrahydrofuran were added to a solution of 3.15 g (12.3 mmol) of N,O-dimethyl 2(S)-(tert-butoxyformamido)-4-pentynohydroxamate in 50 ml of dry tetrahydrofuran at 0° C. under a nitrogen atmosphere. The solution was stirred for 20 minutes and then 40 ml of saturated potassium hydrogen sulphate solution were added dropwise. The mixture was stirred for 15 minutes and then diluted with diethyl ether. The organic layer was dried over magnesium sulphate and evaporated to give an oil which was dissolved in 50 ml of methanolic hydrogen chloride solution. The solution was left at room temperature for 1 hour and then evaporated to dryness to give a dark brown gum. 1.05 g of the gum were added to a solution of 2.06 g (5.84 mmol) of N-[(9-fluorenyl)methoxycarbonyl]-L-leucine, 867 mg (6.42 mmol) of hydroxybenzotriazole, 1.233 g (6.42 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 2.216 g (19.27 mmol) of N-ethylmorpholine in 40 ml of dichloromethane. The solution was stirred at room temperature for 18 hours, washed with 2M hydrochloric acid and saturated sodium bicarbonate solution, dried over magnesium sulphate and evaporated to give a gum which was chromatographed on silica gel using ethyl acetate/petrol (2:3) for the elution. There were obtained 1.1 g of N2-[(9-fluorenyl)methoxycarbonyl]-N1-[1(S)-(dimethoxymethyl)-3-butynyl]-L-leucinamide as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ: 0.86 (6H,dd), 1.35-1.65 (3H,m), 2.22-2.39 (2H,m), 2.75(1H,t), 3.22 (3H,s), 3.27 (3H,s), 3.91 (1H,m), 4.08 (1H,m), 4.15-4.3 (4H,m), 7.29 (2H,m), 7.4 (2H,t), 7.42 (1H,d), 7.71 (2H,d), 7.84 (1H,d), 7.88 (2H,d).

Workup

  1. stirringThe mixture was stirred for 15 minutes
  2. dry with materialThe organic layer was dried over magnesium sulphate
  3. customevaporated
  4. customto give an oil which
  5. waitThe solution was left at room temperature for 1 hour
  6. customevaporated to dryness
  7. customto give a dark brown gum
  8. stirringThe solution was stirred at room temperature for 18 hours
  9. washwashed with 2M hydrochloric acid and saturated sodium bicarbonate solution
  10. dry with materialdried over magnesium sulphate
  11. customevaporated
  12. customto give a gum which
  13. customwas chromatographed on silica gel
  14. washfor the elution

Sources & evidence

ORD record
ord-d0f28f53f97647f1bdbc335c850fb11c
Source dataset
uspto-grants-2000_01
Patent number
US06018020

Reaction notes

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