Benzyl Alcohol → HCID 131724726, compound

HRID 23178Notes

Reaction equation

HRID 23178 reaction equation
[CH3:1][O:2][C:3](=[O:35])[C:4]([NH:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])([S:11]([C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)=[CH:16][CH:15]=1)(=[O:13])=[O:12])[C:5]([CH3:10])([CH3:9])C(O)=O.C([N:38]([CH2:41]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:50])C=CC=CC=1.[CH2:60]([OH:67])[C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1>C1C=CC=CC=1>[F:27][C:24]1[CH:25]=[CH:26][C:21]([O:20][C:17]2[CH:16]=[CH:15][C:14]([S:11]([C:4]([NH:28][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])([C:5]([NH:38][C:41]([O:67][CH2:60][C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)=[O:50])([CH3:9])[CH3:10])[C:3]([O:2][CH3:1])=[O:35])(=[O:12])=[O:13])=[CH:19][CH:18]=2)=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 131724727HCID 131724727, compound

Product 1

HCID 131724726HCID 131724726, compoundYield 75.1%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

To a solution of methyl 2(R/S)-[4-(4-fluorophenoxy)benzenesulfonyl][(ethoxycarbonyl)methyl]amino-3,3-dimethyl-butanedioic acid (2.00 g, 3.91 mmol) and triethylamine (0.6 mL, 4.30 mmol) in 50 mL of benzene at 80° C. was added diphenylphosphoryl azide (0.93 mL, 4.3 mmol). After 4 hours, benzyl alcohol (1.62 mL, 15.6 mmol) was added. After an additional 20 hours, the reaction was cooled to room temperature and partitioned between ethyl acetate and 10% aq. citric acid. The organic layer was washed with sat. aq. sodium bicarbonate, dried over sodium sulfate, and concentrated. The excess benzyl alcohol was removed by kugelrohr distillation at 0.28 torr, 70° C., and the residue was purified by chromatography on silica, eluting with 30% ethyl acetate in hexane, to give methyl 2(R/S)-[4-(4-fluorophenoxy)benzenesulfonyl][(ethoxycarbonyl)methyl]amino-3-(benzyloxycarbonyl)amino-3-methylbutanoate (1.81 g, 75%) as a colorless, viscous oil.

Workup

  1. waitAfter an additional 20 hours
  2. custompartitioned between ethyl acetate and 10% aq. citric acid
  3. washThe organic layer was washed with sat. aq. sodium bicarbonate
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe excess benzyl alcohol was removed by kugelrohr distillation at 0.28 torr, 70° C.
  7. customthe residue was purified by chromatography on silica
  8. washeluting with 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-0b7039dde8fa4750b9c01ac1d0c56483
Source dataset
uspto-grants-2005_02
Patent number
US06849732B2

Reaction notes

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