Benzyl Alcohol → Benzyl (1R,3S,4S)-4-[(tert-butoxycarbonyl)amino]-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentylcarbamate

HRID 1174102Notes

Reaction equation

HRID 1174102 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.[CH2:68]([OH:75])[C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1>C1(C)C=CC=CC=1>[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]([OH:29])[CH2:11][C@H:12]([NH:63][C:66](=[O:51])[O:75][CH2:68][C:69]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1)[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)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 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 42625868Benzyl (1R,3S,4S)-4-[(tert-butoxycarbonyl)amino]-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentylcarbamateYield 23%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of the product from Example 1B (11.3 g, 18.7 mmol) in toluene (190 mL) was treated with DPPA (8.1 mL, 37.6 mmol) and triethylamine (5.2 mL, 37.3 mmol), heated at reflux for 2 hours, treated with benzyl alcohol (5.8 mL, 56.0 mmol), heated at reflux for an additional 16 hours, cooled to 25° C. and concentrated. The residue was treated with a solution of tetrabutylammonium fluoride in THF (94 mL, 1N), stirred at 25° C. for 40 hours and concentrated. The mixture was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel eluting with 50% ethyl acetate in chloroform to give 2.6 g (23% yield) of the higher Rf product by TLC (35% ethyl acetate in dichloromethane).

Workup

  1. temperatureheated
  2. temperatureat reflux for 2 hours
  3. temperatureheated
  4. temperatureat reflux for an additional 16 hours
  5. concentrationconcentrated
  6. additionThe residue was treated with a solution of tetrabutylammonium fluoride in THF (94 mL, 1N)
  7. concentrationconcentrated
  8. customThe mixture was partitioned between ethyl acetate and water
  9. washThe organic phase was washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was chromatographed on silica gel eluting with 50% ethyl acetate in chloroform
  14. customto give 2.6 g (23% yield) of the higher Rf product by TLC (35% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-91b8aaded2304a33a312418807a1b2d0
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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