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

HRID 1174284Notes

Reaction equation

HRID 1174284 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][CH: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 67407170(4R,5S)-5-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-6-phenyl-2-[4-(2-pyridinyl)benzyl]hexanoic acid

Product 1

HCID 86726218benzyl (3R,4S)-4-[(tert-butoxycarbonyl)amino]-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentylcarbamateYield 37.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of the product from Example 107C (22.35 mmol) in toluene (500 mL) was treated with DPPA (5.3 mL, 24.59 mmol) and triethylamine (3.75 mL, 26.90 mmol) was heated at reflux for 2 hours, cooled to 25° C., treated with benzyl alcohol (6.9 mL, 66.68 mmol), heated at reflux for an additional 16 hours, cooled and concentrated. A solution of the concentrate in THF (100 mL) was treated with TBAF solution in THF (67 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, to give the title compound (4.98 g, 37% yield), which was used without further purification.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 hours
  3. temperatureheated
  4. temperatureat reflux for an additional 16 hours
  5. temperaturecooled
  6. concentrationconcentrated
  7. concentrationA solution of the concentrate in THF (100 mL)
  8. additionwas treated with TBAF solution in THF (67 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

Sources & evidence

ORD record
ord-c9a559c4f854421293b62f43d2d9bcd9
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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