2-Mercaptobenzoic Acid → HCID 58815986, compound

HRID 2245879Notes

Reaction equation

HRID 2245879 reaction equation
C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:31]([O:33][C:34]([CH:36]1[CH2:41][CH2:40][N:39]([C:42](=[O:68])[C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([C@@H:49]([N:57]3[CH2:62][C@@H:61]([CH3:63])[N:60](CC=C)[CH2:59][C@@H:58]3[CH3:67])[C:50]3[CH:55]=[CH:54][CH:53]=[C:52]([OH:56])[CH:51]=3)[CH:44]=2)[CH2:38][CH2:37]1)=[O:35])[CH3:32].C(O)(=O)C1C(=CC=CC=1)S>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:31]([O:33][C:34]([CH:36]1[CH2:41][CH2:40][N:39]([C:42](=[O:68])[C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([C@@H:49]([N:57]3[CH2:62][C@@H:61]([CH3:63])[NH:60][CH2:59][C@@H:58]3[CH3:67])[C:50]3[CH:55]=[CH:54][CH:53]=[C:52]([OH:56])[CH:51]=3)[CH:44]=2)[CH2:38][CH2:37]1)=[O:35])[CH3:32]

Participants

7

Reactant 3

HCID 54432-Mercaptobenzoic AcidHCID 821241,4-Bis(diphenylphosphino)butaneHCID 12004031HCID 12004031, compound

Product 1

HCID 58815986HCID 58815986, compoundYield 90.3%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Bis(dibenzylideneacetone)palladium (398 mg) was added to a solution of 1,4-bis(diphenylphosphino)butane (295 mg) in THF (7.3 mL) under nitrogen at room temperature for 10 minutes. The resulting Pd-catalyst was transferred to the solution of 1-{3-[(R)-((2S,5R)-4-allyl-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-benzoyl}-piperidine-4-carboxylic acid ethyl ester (3.6 g, Ex. 58) and thiosalicylic acid (1.71 g) in THF (40 mL) via a syringe. The reaction was stirred under nitrogen at room temperature for overnight. The reaction mixture was concentrated under vacuum. EtOAc (75 mL) was added to the residue, followed by the addition of 1 N aqueous HCl (110 mL). The EtOAc layer and acidic water layer were separated. The acidic water layer was extracted with EtOAc (50 mL×2). The acidic water layer was neutralized with saturated NaHCO3 solution to pH≅8 and then extracted with n-butanol (75 mL×3). The combined n-butanol layer was washed with water (60 mL) and concentrated to give crude product, 1-{3-[(R)-((2S,5R)-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-benzoyl}-piperidine-4-carboxylic acid ethyl ester (3.0 g). 1H NMR (300 MHz, CD3OD) δ 7.55-7.37 (m, 3H), 7.27 (m, 1H), 7.18 (dd, J=8.0, 8.0, 1H), 6.71 (m, 2H), 6.61 (s, 1H), 5.36 (s, 1H), 4.44 (m, 1H), 4.14 (q, J=7.0 Hz, 2H), 3.68 (m, 1H), 3.08 (m, 2H), 2.89 (m, 2H), 2.65 (m, 2H), 2.46 (m, 1H), 2.00 (m, 1H), 1.84 (m, 1H), 1.76-1.45 (m, 3H), 1.25 (t, J=7.0 Hz, 3H), 1.21 (d, J=6.0 Hz, 3H), 0.96 (d, J=6.5, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. additionEtOAc (75 mL) was added to the residue
  3. additionfollowed by the addition of 1 N aqueous HCl (110 mL)
  4. customThe EtOAc layer and acidic water layer were separated
  5. extractionThe acidic water layer was extracted with EtOAc (50 mL×2)
  6. extractionextracted with n-butanol (75 mL×3)
  7. washThe combined n-butanol layer was washed with water (60 mL)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-d51e2112631a41ec862f38ec1a747a2c
Source dataset
uspto-grants-2010_03
Patent number
US07683168B2

Reaction notes

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