Ethyl Acetate → (1s,2r)-4'-(2-Benzyloxy-1-benzyloxycarbamoyl-propylcarbamoyl)-biphenyl-4-carboxylic acid

HRID 1692511Notes

Reaction equation

HRID 1692511 reaction equation
[OH:1][C@@H:2]1[CH2:6]C[N:4]([C:7]([C:9]2[CH:14]=[CH:13][C:12](OC(F)(F)F)=[CH:11][CH:10]=2)=[O:8])[C@H:3]1[C:20]([NH:22][O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:21].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)[C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=2N=N1.CCN(C(C)C)C(C)C.O[C@H](C)[C@H](N[C:75]([C:77]1[CH:82]=[CH:81][C:80](C(C2C=CC=CC=2)=O)=[CH:79][CH:78]=1)=O)C(OC)=O.CC[O:94][C:95](C)=[O:96]>CN(C=O)C>[CH2:75]([O:1][C@H:2]([CH3:6])[C@H:3]([NH:4][C:7]([C:9]1[CH:10]=[CH:11][C:12]([C:41]2[CH:42]=[CH:43][C:44]([C:95]([OH:96])=[O:94])=[CH:45][CH:46]=2)=[CH:13][CH:14]=1)=[O:8])[C:20](=[O:21])[NH:22][O:23][CH2:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[C:77]1[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=1

Participants

7

Reactant 5

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 59697585methyl(2S,3R)-3-hydroxy-2-{[4-(phenylcarbonyl)phenyl]carbonylamino}butanoateHCID 59697601((2r,3r)-3-Hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl}pyrrolidin-2-yl)-n-(phenylmethoxy)carboxamide

Product 1

HCID 87102973(1s,2r)-4'-(2-Benzyloxy-1-benzyloxycarbamoyl-propylcarbamoyl)-biphenyl-4-carboxylic acidYield 13%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of 4,4′-biphenyldicarboxylic acid 2 (1.360 g, 5.61 mmol) in DMF (180 mL) was added BOP (2.007 g, 4.54 mmol) and DIEA (1.7 mL, 9.8 mmol). A solution of (1S,2R)-2-amino-3,N-bis-benzyloxy-butyramide 1 (944 mg, 3.00 mmol) in DMF (20 mL) was added and the reaction stirred for 18 h. The solution was diluted with EtOAc (250 mL) and washed with 1.0 M HCl (500 mL). The aqueous layer was extracted with EtOAc (250 mL) and the organic layers combined. The organic layer was washed with 1.0 M HCl (250 mL), dried over MgSO4, and concentrated to give a crude yellow solid. Purification by silica gel chromatography (60:1 CH2Cl2/MeOH) gave 210 mg (1S,2R)-4′-(2-benzyloxy-1-benzyloxycarbamoyl-propylcarbamoyl)-biphenyl-4-carboxylic acid 3. (13% yield) as a yellow solid. Rf=0.80 (10:1 CH2Cl2/MeOH); LRMS (ES+) m/z 539.1 (C32H30N2O6+H requires 539.22).

Workup

  1. washwashed with 1.0 M HCl (500 mL)
  2. extractionThe aqueous layer was extracted with EtOAc (250 mL)
  3. washThe organic layer was washed with 1.0 M HCl (250 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customto give a crude yellow solid
  7. customPurification by silica gel chromatography (60:1 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-a76cc6dac08c4b7cad3daf2beff2cae6
Source dataset
uspto-grants-2012_04
Patent number
US08153843B2

Reaction notes

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