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

HRID 1174101노트

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HRID 1174101 반응식
[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]

참가 물질

6

반응물 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

생성물 1

HCID 11548871Benzyl (1S,3S,4S)-4-[(tert-butoxycarbonyl)amino]-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentylcarbamate수율 38%

시약·촉매·용매 1

HCID 1140Toluene용매

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온도
25 °C

실험 절차

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 TBAF 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 4.2 g (38% yield) of the lower Rf product by TLC (35% ethyl acetate in dichloromethane).

후처리

  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 TBAF 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 4.2 g (38% yield) of the lower Rf product by TLC (35% ethyl acetate in dichloromethane)

출처 및 근거

ORD 기록
ord-805b956b889949e68822a1a845bec1eb
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07834043B2

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