Dimethylformamide → HCID 69939144, compound

HRID 1058268Notes

Reaction equation

HRID 1058268 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:11]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:12]=1[CH2:13][NH:14][C:15](=[O:21])[C@@H:16]1[CH2:20][CH2:19][CH2:18][NH:17]1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1[CH2:33][CH2:32][O:31]CC1.CN([P+](ON1N=N[C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][C:46]1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.CN(C=[O:65])C>>[OH:65][C@H:33]([CH:46]1[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]1)[C:32]([N:17]1[CH2:18][CH2:19][CH2:20][C@H:16]1[C:15]([NH:14][CH2:13][C:12]1[CH:22]=[C:23]([Cl:26])[CH:24]=[CH:25][C:11]=1[CH:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH3:10])=[O:21])=[O:31]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 23560072HCID 23560072, compound

Product 1

HCID 69939144HCID 69939144, compound

Procedure

To a stirred solution of L-prolin-N-(2-(1-tert-butyloxycarbonylaminoethyl)-5-chlorobenzyl)amide from the previous step (54.6 mg, 0.143 mmol), R-(−)-hexahydromandelic acid(22.62 mg, 0.143 mmol), and NMM (16 μL, 0.143 mmol) in DMF (5 mL) at ambient temperature under nitrogen atmosphere was added BOP reagent (76 mg, 0.172 mmol). The mixture was stirred at ambient temperature for 3 h. The solvent was removed under reduced pressure. The residue was partitioned between EtOAc and saturated aqueous NaHCO3. The EtOAc layer was separated, dried over anhydrous Na2SO4, and filtered. The filtrate solvent was removed under reduced pressure and the residue was purified by preparative thick layer silica gel plate chromatography (2000 μM×20 cm×20 cm) developed with 7.5% MeOH in dichloromethane. Desired bands were removed and eluted with 5% MeOH in dichloromethane which were concentrated in vacuo to obtain 1-((2R)-2-hydroxy-2-cyclohexylethanoyl)-N-(2-(1-(tert-butyloxycarbonylamino)ethyl)-5-chlorobenzyl)-L-prolinamide as a clear colorless oil (40 mg; HPLC RT=3.51 min, method A; LC-MS m/z=522.1).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customThe residue was partitioned between EtOAc and saturated aqueous NaHCO3
  3. customThe EtOAc layer was separated
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customThe filtrate solvent was removed under reduced pressure
  7. customthe residue was purified by preparative thick layer silica gel plate chromatography (2000 μM×20 cm×20 cm)
  8. customDesired bands were removed
  9. washeluted with 5% MeOH in dichloromethane which
  10. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-9b7c584bf7014abba2083b2b980a823c
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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