tert-Butanol → tert-butyl(1S,2S,4S)-1-benzyl-4-[(tert-butoxycarbonyl)amino]-2-hydroxy-5-[4-(2-pyridinyl)phenyl]pentylcarbamate

HRID 1174341Notes

Reaction equation

HRID 1174341 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C@@H:10]([O:29][Si](C(C)(C)C)(C)C)[CH2:11][CH:12]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)=[CH:19][CH:18]=1)C(O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:51])=CC=1.C([N:63]([CH2:66]C)CC)C.[C:68]([OH:72])([CH3:71])([CH3:70])[CH3:69]>C1(C)C=CC=CC=1.CN(C1C=CN=CC=1)C>[CH2:37]([C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C@@H:10]([OH:29])[CH2:11][C@@H:12]([NH:63][C:66]([O:72][C:68]([CH3:71])([CH3:70])[CH3:69])=[O:51])[CH2:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)=[CH:21][CH:22]=1)[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 8471Triethylamine2×HCID 199401P,P-Diphenylphosphinic azideHCID 67406695(4S,5S)-5-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-6-phenyl-2-(4-pyridin-2-ylbenzyl)hexanoic acid

Product 1

HCID 86726240tert-butyl(1S,2S,4S)-1-benzyl-4-[(tert-butoxycarbonyl)amino]-2-hydroxy-5-[4-(2-pyridinyl)phenyl]pentylcarbamateYield 9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of the product from Example 1B (7.32 g, 12.1 mmol) in toluene (400 mL) were treated with DPPA (5.2 mL, 24.2 mmol) and triethylamine (3.4 mL, 24.4 mmol), heated at reflux for 2 hours, cooled, treated with tert-Butyl alcohol (41.6 mL), triethylamine (4 mL), and DMAP (0.30 g), heated at reflux for an additional 64 hours, cooled and concentrated. A solution of the residue in THF (60 mL) was treated with TBAF solution in THF (36 mL, 1N), stirred at 25° C. for 40 hours, concentrated and partitioned between ethyl acetate and water. The organic phase was washed with brined, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel eluting with 0-50% ethyl acetate in dichloromethane to give 0.614 g (9% yield) of the lower Rf product by TLC (25% ethyl acetate in dichloromethane).

Workup

  1. temperatureheated
  2. temperatureat reflux for 2 hours
  3. temperaturecooled
  4. temperatureheated
  5. temperatureat reflux for an additional 64 hours
  6. temperaturecooled
  7. concentrationconcentrated
  8. additionA solution of the residue in THF (60 mL) was treated with TBAF solution in THF (36 mL, 1N)
  9. concentrationconcentrated
  10. custompartitioned between ethyl acetate and water
  11. washThe organic phase was washed with brined,
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe residue was chromatographed on silica gel eluting with 0-50% ethyl acetate in dichloromethane
  16. customto give 0.614 g (9% yield) of the lower Rf product by TLC (25% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-d8deff89fa68467a9e438849b981bae5
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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