Hydrochloric Acid → HCID 70098728, compound

HRID 566793Notes

Reaction equation

HRID 566793 reaction equation
C([O:5][C:6](=[O:43])[CH2:7][C@@H:8]([C:26]1([C:31]2[CH:36]=[CH:35][C:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[CH:33][CH:32]=2)[CH:30]=[CH:29][NH:28][CH2:27]1)[C:9]([NH:11]N1[C@@H](CC2C=CC=CC=2)COC1(C)C)=[O:10])(C)(C)C.[Li+].[OH-].[CH3:46][CH2:47][OH:48].Cl>C1COCC1.O>[CH2:26]([C@H:46]([NH:11][C:9](=[O:10])[C@H:8]([C:26]1([C:31]2[CH:32]=[CH:33][C:34]([C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=3)=[CH:35][CH:36]=2)[CH:30]=[CH:29][NH:28][CH2:27]1)[CH2:7][C:6]([OH:5])=[O:43])[CH2:47][OH:48])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 3939Lithium HydroxideHCID 70097970HCID 70097970, compound

Product 1

HCID 70098728HCID 70098728, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-(4(S)-benzyl-2,2-dimethyl-oxazolidin-3-yl)-3(S)-[3-(biphenyl-4-yl)-1H-pyrrol-3-yl]succinamic acid t-butyl ester (80 mg, 0.14 mmol) in THF (5 mL) was added 2M aqueous LiOH (5 mL). EtOH (few drops) and H2O were added until a homogeneous solution was obtained. The resultant solution was heated at 50° C. After 12 hours, the mixture was acidified with 6N HCl to pH1. After another 5.5 hours at 50° C., the mixtrue was partitioned between EtOAc and 1 M pH 7 phosphate buffer. The aqueousueous phase was separated and extracted with EtOAc two times. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated to a residue which, upon trituration with CH2Cl2/hex, provided 32 mg (49%) of pure N-(1(S)-benzyl-2-hydroxyethyl)-3(S)-[3-(biphenyl-4-yl)-1H-pyrrol-3-yl]succinarnic acid as a white solid, mp 151-4° C. 1H NMR: (DMSO-d6): δ 7.83 (d, 1H, J=8.5 Hz), 7.74 (d, 2H, J=8.8 Hz), 7.69 (d, 2H, J=7.4 Hz), 7.59 (d, 2H, J=8.8 Hz), 7.46 (t, 2H, J=7.4 Hz), 7.38-7.31 (m, 2H), 7.28-7.13 (m, 6H), 6.22 (s, 1H), 4.81-4.70 (m, 1H), 3.89-3.78 (m, 2H), 2.85-2.69 (m, 2H). Anal. Calculated for C29H28N2O4•0.4 H2O: C, 73.21; H, 6.10; N, 5.89. Found: C, 73.39; H, 6.09; N, 5.93.

Workup

  1. customwas obtained
  2. waitAfter another 5.5 hours at 50° C.
  3. customthe mixtrue was partitioned between EtOAc and 1 M pH 7 phosphate buffer
  4. customThe aqueousueous phase was separated
  5. extractionextracted with EtOAc two times
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated to a residue which, upon trituration with CH2Cl2/hex

Sources & evidence

ORD record
ord-cbafc4f39d764a1e8e135c64ce108b5f
Source dataset
uspto-grants-2001_01
Patent number
US06174915B1

Reaction notes

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