Benzyl Alcohol → tert-butyl (1S,2S,4S)-1-benzyl-4-{[benzyloxycarbonyl]amino}-5-(4-bromophenyl)-2-{[tert-butyl(dimethyl)silyl]oxy}pentylcarbamate

HRID 1174264Notes

Reaction equation

HRID 1174264 reaction equation
[Br:1][C:2]1[CH:38]=[CH:37][C:5]([CH2:6][CH:7]([CH2:11][C@H:12]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[C@@H:13]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)C(O)=O)=[CH:4][CH:3]=1.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:46])=CC=1.C([N:58]([CH2:61]C)CC)C.[CH2:63]([OH:70])[C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1>C1(C)C=CC=CC=1>[CH2:14]([C@H:13]([NH:21][C:22](=[O:23])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[C@@H:12]([O:29][Si:30]([C:33]([CH3:34])([CH3:35])[CH3:36])([CH3:32])[CH3:31])[CH2:11][C@@H:7]([NH:58][C:61]([O:70][CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1)=[O:46])[CH2:6][C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:38][CH:37]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 67408601(4S,5S)-2-(4-bromobenzyl)-5-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-6-phenylhexanoic Acid

Product 1

HCID 86726209tert-butyl (1S,2S,4S)-1-benzyl-4-{[benzyloxycarbonyl]amino}-5-(4-bromophenyl)-2-{[tert-butyl(dimethyl)silyl]oxy}pentylcarbamateYield 18%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of the product from Example 92C (14.1 g, 23.3 mmol) in toluene (230 mL) was treated with DPPA (10.0 mL, 46.4 mmol) and triethylamine (6.5 mL, 46.6 mmol), heated at reflux for 2 hours, treated with benzyl alcohol (7.2 mL, 69.9 mmol), heated at reflux for an additional 16 hours, cooled and concentrated. The residue was purified by chromatography on silica gel, eluting with 20% ethyl acetate in hexanes to give the higher Rf product (2.94 g, 18% yield).

Workup

  1. temperatureheated
  2. temperatureat reflux for 2 hours
  3. temperatureheated
  4. temperatureat reflux for an additional 16 hours
  5. temperaturecooled
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography on silica gel
  8. washeluting with 20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-12480c16c64c4bb99df1a16dd26b8d2c
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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