1,2-Dichloroethane → HCID 131724783, compound

HRID 984428Notes

Reaction equation

HRID 984428 reaction equation
[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7]([OH:9])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.N[CH:32]([CH2:57][CH:58]([F:60])[F:59])[C:33](=[O:56])[C:34](=[P:37]([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C:35]#[N:36]>ClCCl>[NH:1]([C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])[C@H:2]([C:7]([OH:9])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5].[F:60][CH:58]([F:59])[CH2:57][CH2:32][C:33](=[O:56])[C:34](=[P:37]([C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)([C:50]1[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:35]#[N:36]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-HCID 22558303HCID 22558303, compound

Product 1

HCID 131724783HCID 131724783, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Synthesis of compound 15 (see scheme 7) Boc-Leu-OH (1.16 g, 5 mmol) was dissolved in dichloromethane (50 mL) and EDC (1.05 g, 5.5 mmol) and HOBt (743 mg, 5.5 mmol) were added. The resulting solution was cooled to 0° C. and (±)-4-Amino-6,6-difluoro-3-oxo-2-triphenylphosphoranylidene-hexanenitrile (2.32 g, 5.5 mmol) was added in one portion. The ice bath was removed and the mixture stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane (100 mL) and washed successively with 1 N aqueous HCl, water, saturated aqueous NaHCO3 and brine. Drying (Na2SO4) and evaporation gave 2.7 g (85%) of Boc-Leu-6,6-difluoro-3-oxo-2-triphenylphosphoranylidene-hexanenitrile as a yellowish foam. The foregoing compound (2.7 g, 4.2 mmol) was dissolved in dichloromethane/methanol (40 ml, 7:3, v/v) and cooled to −78° C. Ozone was bubbled through the solution until the blue color remained. The solution was then purged with nitrogen and 12 mL of MeOH were added, the resulting solution was stirred at −78° C. for 30 min. and at room temperature for 2 h. Evaporation gave a light yellow oil, which was dissolved in MeOH (6 mL) and the resulting solution was cooled to 0° C. After addition portionwise of NaBH4 (159 mg, 4.2 mmol) the resulting reaction mixture was stirred at 0° C. for 2 hours, poured into saturated aqueous NaHCO3 and extracted with EtOAc. The combined organic layers were washed with brine and dried (Na2SO4). Evaporation gave a solid which was purified by flash chromatography (PE/ethyl acetate 3:2) to give 832 mg (50%) of the Boc protected dipeptide hydroxyester.

Workup

  1. customThe ice bath was removed
  2. additionThe reaction mixture was diluted with dichloromethane (100 mL)
  3. washwashed successively with 1 N aqueous HCl, water, saturated aqueous NaHCO3 and brine
  4. customDrying
  5. custom(Na2SO4) and evaporation

Sources & evidence

ORD record
ord-a48ec1eab4c84be0a0351f10a164e41d
Source dataset
uspto-grants-2005_03
Patent number
US06867284B1

Reaction notes

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