Tetrahydrofuran → Boc-D-Phe-D-Leu-OBn

HRID 1399503

Reaction equation

HRID 1399503 reaction equation
[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@@H:2]([C:10]([OH:12])=O)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH:20]1[CH:25]=[C:24]2N=NN(O)[C:23]2=[CH:22][CH:21]=1.[OH2:30].CC[N:33]([CH:37]([CH3:39])[CH3:38])C(C)C.CCN=C=N[CH2:45][CH2:46][CH2:47]N(C)C.C1[CH2:55][O:54]CC1>>[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@@H:2]([C:10]([NH:33][C@@H:37]([C:38]([O:54][CH2:55][C:24]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:25]=1)=[O:30])[CH2:39][CH:46]([CH3:47])[CH3:45])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 637610Boc-D-phenylalanineHCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 89802875Boc-D-Phe-D-Leu-OBn

Procedure

To a suspension of Boc-D-Phe-OH intermediate I-1 (7.96 g, 30.0 mmol), D-Leu-OBn p-TsOH intermediate 1-2 (11.80 g, 30.0 mmol), HOBt monohydrate (4.46 g, 33.0 mmol) and DIEA (8.53 g, 66.0 mmol) in anhydrous THF (250 mL) cooled in an ice-water bath was added EDCI (6.33 g, 33.0 mmol) in four portions over 20 minutes with 5 minutes between each addition. The suspension was stirred overnight from a starting temperature of 0° C. to room temperature. After evaporation of THF, the residue was dissolved in ethyl acetate and washed sequentially with 10% citric acid, saturated NaHCO3 and water. The organic phase was dried over sodium sulfate and evaporated under reduced pressure. The residue was dissolved in DCM, passed through a silica gel plug and eluted with 20% ethyl acetate in hexanes. Eluant was evaporated to give the pure Boc-D-Phe-D-Leu-OBn, intermediate 1-3 (12.40 g, 88%) as a clear oil. LC-MS: m/z=469 (MH).

Workup

  1. temperaturecooled in an ice-water bath
  2. additionbetween each addition
  3. customAfter evaporation of THF
  4. dissolutionthe residue was dissolved in ethyl acetate
  5. washwashed sequentially with 10% citric acid, saturated NaHCO3 and water
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. customevaporated under reduced pressure
  8. dissolutionThe residue was dissolved in DCM
  9. washeluted with 20% ethyl acetate in hexanes
  10. customEluant was evaporated

Sources & evidence

ORD record
ord-b859fbeb81e6465195288da7f1ff0ec3
Source dataset
uspto-grants-2014_12
Patent number
US08906859B2

Linked notes

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