Hydrochloric Acid → 6-((1S,3R)-1-biphenyl-4-ylmethyl-3-carboxy-butylcarbamoyl)-4-oxo-4H-pyran-2-carboxylic acid

HRID 2384023Notes

Reaction equation

HRID 2384023 reaction equation
C([O:8][C:9]([C@H:11]([CH3:40])[CH2:12][C@H:13]([NH:27][C:28]([C:30]1[O:35][C:34]([C:36]([OH:38])=[O:37])=[CH:33][C:32](=[O:39])[CH:31]=1)=[O:29])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:17][CH:16]=1)=[O:10])C1C=CC=CC=1.B(Cl)(Cl)Cl.Cl>C(Cl)Cl>[C:18]1([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:19]=[CH:20][C:15]([CH2:14][C@@H:13]([NH:27][C:28]([C:30]2[O:35][C:34]([C:36]([OH:38])=[O:37])=[CH:33][C:32](=[O:39])[CH:31]=2)=[O:29])[CH2:12][C@H:11]([C:9]([OH:10])=[O:8])[CH3:40])=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 25135Boron TrichlorideHCID 866482066-((1S,3R)-3-benzyloxycarbonyl-1-biphenyl-4-ylmethyl-butylcarbamoyl)-4-oxo-4H-pyran-2-carboxylic acid

Product 1

HCID 596081716-((1S,3R)-1-biphenyl-4-ylmethyl-3-carboxy-butylcarbamoyl)-4-oxo-4H-pyran-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Next, to a solution of 6-((1S,3R)-3-benzyloxycarbonyl-1-biphenyl-4-ylmethyl-butylcarbamoyl)-4-oxo-4H-pyran-2-carboxylic acid (100 mg, 0.185 mmol) in methylene chloride (5 mL) is added BCl3 (65.1 mg, 0.556 mmol) and the mixture is stirred at room temperature for 10 minutes. The mixture is acidified to pH 2-3 with aqueous 1M HCl and is extracted with ethyl acetate. The organic phase is washed with water and brine and is dried over magnesium sulfate. The solvent is removed under reduced pressure and the residue is purified by preparative HPLC using a gradient of 10-100% MeCN/water (0.1% TFA) to elute the product. The proper fractions are lyophilized to furnish 6-((1S,3R)-1-biphenyl-4-ylmethyl-3-carboxy-butylcarbamoyl)-4-oxo-4H-pyran-2-carboxylic acid. MS 450.1 (M+1); 1H-NMR (400 Hz, DMSO-d6); δ ppm 1.07 (d, J=7.07 Hz, 3H), 1.59 (m, 1H), 1.88 (m, 1H), 2.45 (m, 1H), 2.84 (d, J=6.69 Hz, 2H), 4.19 (m, 1H), 6.84 (s, 1H), 6.93 (s, 1H), 7.32 (dd, J=8.08 Hz, 6.57 Hz, 3H), 7.45 (t, J=7.83 Hz, 2H), 7.58 (d, J=8.21 Hz, 2H), 7.64 (d, J=7.33 Hz, 2H), 8.61 (d, J=8.72 Hz, 1H).

Workup

  1. extractionis extracted with ethyl acetate
  2. washThe organic phase is washed with water and brine
  3. dry with materialis dried over magnesium sulfate
  4. customThe solvent is removed under reduced pressure
  5. customthe residue is purified by preparative HPLC
  6. washto elute the product

Sources & evidence

ORD record
ord-6407f1d5e26244a4be1d42a5862cd292
Source dataset
uspto-grants-2012_09
Patent number
US08263629B2

Reaction notes

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