Hydrochloric Acid → HCID 70098728, compound

HRID 613900Notes

Reaction equation

HRID 613900 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 mixture was partitioned between EtOAc and 1M 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]succinamic 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 mixture was partitioned between EtOAc and 1M 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-3223c4a3c9714741b6e5d467cfa29953
Source dataset
uspto-grants-1999_12
Patent number
US06008243

Reaction notes

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