1,2-Dichloroethane → 3(S)-(2-((2(S)-Benzoylamino-3-methylbutyryl)benzylamino)acetylamino)-4-(4-(2,6-dichlorophenyl)-oxazol-2-yl)-4-hydroxybutyric Acid tert-Butyl Ester

HRID 1456651Notes

Reaction equation

HRID 1456651 reaction equation
[C:1]([NH:9][C@@H:10]([CH:25]([CH3:27])[CH3:26])[C:11]([N:13]([CH2:21][C:22](O)=[O:23])[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:28]([O:32][C:33](=[O:58])[CH:34](N)[C@H:35](C(OCC=C)=O)[CH:36]([C:38]1[O:39][CH:40]=[C:41]([C:43]2[C:48]([Cl:49])=[CH:47][CH:46]=[CH:45][C:44]=2[Cl:50])[N:42]=1)[OH:37])([CH3:31])([CH3:30])[CH3:29].C([SnH](CCCC)CCCC)CCC.C1C=CC2N(O)N=[N:78]C=2C=1.C(Cl)CCl>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN(C=O)C.C(Cl)Cl>[C:28]([O:32][C:33](=[O:58])[CH2:34][C@H:35]([NH:78][C:22](=[O:23])[CH2:21][N:13]([C:11](=[O:12])[C@@H:10]([NH:9][C:1](=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH:25]([CH3:27])[CH3:26])[CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[CH:36]([C:38]1[O:39][CH:40]=[C:41]([C:43]2[C:48]([Cl:49])=[CH:47][CH:46]=[CH:45][C:44]=2[Cl:50])[N:42]=1)[OH:37])([CH3:31])([CH3:30])[CH3:29]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 5948TributylstannaneHCID 757711-HydroxybenzotriazoleHCID 53859725((2(S)-Benzoylamino-3-methylbutyryl)benzylamino)acetic AcidHCID 697241953(S)-(Allyloxycarbonyl)-amino-4-((2,6-dichloro-phenyl)oxazol-2-yl)-4-hydroxy-butyric Acid tert-Butyl Ester

Product 1

HCID 544408483(S)-(2-((2(S)-Benzoylamino-3-methylbutyryl)benzylamino)acetylamino)-4-(4-(2,6-dichlorophenyl)-oxazol-2-yl)-4-hydroxybutyric Acid tert-Butyl EsterYield 26.1%

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of compound 704 (318 mg, 0.86 mmol) and compound 707 (370 mg, 0.78 mmol) in 1:1 CH2Cl2 :DMF (8.0 mL) was added bis(triphenylphosphine) palladium dichloride (10 mg), followed by the dropwise addition of tri-n-butyl tin hydride (320 μL, 1.19 mmol). After the addition was complete, HOBT (212 mg, 1.57 mmol) was added and the reaction was cooled to 0° C. added EDC (180 mg, 0.94 mmol) was added and the reaction allowed to warm to rt and stir overnight. The reaction was concentrated in vacuo and the residue taken up into EtOAc and sat. aq. KHSO4. The layers were separated and the organic phase was washed with sat. aq. K2CO3, brine, dried over MgSO4, filtered and concentrated in vacuo. Chromatography on silica gel (elution with 2% MeOH:CH2Cl2) provided 150 mg of compound 708. ##STR87##

Workup

  1. additionAfter the addition
  2. additionwas added
  3. temperatureto warm to rt
  4. concentrationThe reaction was concentrated in vacuo
  5. customThe layers were separated
  6. washthe organic phase was washed with sat. aq. K2CO3, brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9f4afc31feb3492c8557e0a369a863f2
Source dataset
uspto-grants-1998_12
Patent number
US05843904

Reaction notes

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