Triethylamine → (1S,2S)-(1-([benzyloxycarbonyl-(2,4-dimethyl-benzyl)-amino]-methyl}-2-hydroxy-pentyl)-carbamic acid tert-butyl ester

HRID 1766830Notes

Reaction equation

HRID 1766830 reaction equation
[CH2:1]([O:8][C:9](=[O:26])[NH:10][CH2:11][C@H:12]([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C@@H:13]([OH:17])[C:14]#[C:15][CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:27][C:28]1[CH:35]=[C:34]([CH3:36])[CH:33]=[CH:32][C:29]=1[CH:30]=O.C([BH3-])#N.[Na+].C(N(CC)CC)C.C(OC(OC(OCC1C=CC=CC=1)=O)=O)C1C=CC=CC=1>CO.[Pd]>[C:22]([O:21][C:19](=[O:20])[NH:18][C@@H:12]([CH2:11][N:10]([C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:26])[CH2:30][C:29]1[CH:32]=[CH:33][C:34]([CH3:36])=[CH:35][C:28]=1[CH3:27])[C@@H:13]([OH:17])[CH2:14][CH2:15][CH3:16])([CH3:25])([CH3:24])[CH3:23]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 618142,4-DimethylbenzaldehydeHCID 3649378Dibenzyl PyrocarbonateHCID 5003444Sodium cyanoborohydrideHCID 67271362(2S,3S)-(2-tert-butoxycarbonylamino-3-hydroxy-hex-4-ynyl)-carbamic acid benzyl ester

Product 1

HCID 69287833(1S,2S)-(1-([benzyloxycarbonyl-(2,4-dimethyl-benzyl)-amino]-methyl}-2-hydroxy-pentyl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of {(2S,3S)-(2-tert-butoxycarbonylamino-3-hydroxy-hex-4-ynyl)-carbamic acid benzyl ester (1.7 g, 4.8 mmol, prepared as described in WO PCT 0250019) in MeOH (72 mL) was charged with 5% Pd/C, Degussa style (350 mg), stirred under H2 (1 atm) for 12 h at RT, filtered, and concentrated in vacuo. The residue was dissolved in MeOH (47 mL). The resultant solution was charged sequentially with 2,4-dimethylbenzaldehyde (0.66 mL, 4.7 mmol) and sodium cyanoborohydride (360 mg, 5.7 mmol), stirred for 12 h at RT, quenched with sat. NaHCO3, and extracted twice with EtOAc. The organic extracts were combined, washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was dissolved in THF (66 mL). The resultant solution was charged sequentially with triethylamine (1.2 mL, 9.0 mmol) and dibenzyldicarbonate (1.5 g, 5.4 mmol), stirred for 36 h at RT, quenched with sat. NH4Cl, and extracted twice with EtOAc. The organic extracts were combined, washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford (1S,2S)-(1-([benzyloxycarbonyl-(2,4-dimethyl-benzyl)-amino]-methyl}-2-hydroxy-pentyl)-carbamic acid tert-butyl ester as a clear and colorless oil (2.0 g, 86% yield). MS found: (M+Na)+=507.4.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in MeOH (47 mL)
  4. stirringstirred for 12 h at RT
  5. customquenched with sat. NaHCO3
  6. extractionextracted twice with EtOAc
  7. washwashed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. dissolutionThe residue was dissolved in THF (66 mL)
  12. stirringstirred for 36 h at RT
  13. customquenched with sat. NH4Cl
  14. extractionextracted twice with EtOAc
  15. washwashed with brine
  16. dry with materialdried (Na2SO4)
  17. filtrationfiltered
  18. concentrationconcentrated in vacuo
  19. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-95c65b1f1313401daa877410af5be5f4
Source dataset
uspto-grants-2007_06
Patent number
US07230133B2

Reaction notes

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