Hydrochloric Acid → HCID 44224066, compound

HRID 451646Notes

Reaction equation

HRID 451646 reaction equation
B(Br)(Br)Br.C[O:6][C:7]1[C:16]2[CH:15]=[C:14]([O:17]C)[C:13]([O:19]C)=[C:12]([C:21]([NH:23][CH2:24][CH:25]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH3:26])=[O:22])[C:11]=2[CH:10]=[C:9]([CH3:33])[C:8]=1[C:34]1[C:43]([CH3:44])=[CH:42][C:41]2[C:40]([C:45]([NH:47][CH2:48][CH:49]([C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)[CH3:50])=[O:46])=[C:39]([O:57]C)[C:38]([O:59]C)=[CH:37][C:36]=2[C:35]=1[O:61]C.Cl>C(Cl)Cl>[OH:6][C:7]1[C:16]2[CH:15]=[C:14]([OH:17])[C:13]([OH:19])=[C:12]([C:21]([NH:23][CH2:24][CH:25]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH3:26])=[O:22])[C:11]=2[CH:10]=[C:9]([CH3:33])[C:8]=1[C:34]1[C:43]([CH3:44])=[CH:42][C:41]2[C:40]([C:45]([NH:47][CH2:48][CH:49]([C:51]3[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=3)[CH3:50])=[O:46])=[C:39]([OH:57])[C:38]([OH:59])=[CH:37][C:36]=2[C:35]=1[OH:61]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 25134Boron tribromideHCID 44191538HCID 44191538, compound

Product 1

HCID 44224066HCID 44224066, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

0.65 mL of BBr3 solution (1.72 g, 6.85 mmol) was added dropwise into a solution of compound 7 (420 mg, 0.55 mmol) in 20 mL of anhydrous CH2Cl2 at −78° C. Stirring was continued at −78° C. for 1 h, 0° C. for 1 h, and ambient temperature for 1 h. 50 grams of ice containing 10 mL of 6M HCl was added to the mixture and stirred for 30 min at room temperature. The aqueous layer was extracted with ethyl acetate (3×60 mL). The combined organic layer was washed with water, brine and dried over MgSO4. The solvent was concentrated in vacuo and the residue was purified using C-18 column chromatography followed by preparative HPLC (H2O/Acetonitrile) to give 150 mg of compound 9 (39%) as white-yellow solid. 1H NMR (600 MHz, CD3OD) δ 7.39 (d, J=4.2 Hz, 2H), 7.19 (m, 4H), 7.15 (t, J1=6.0 Hz, J2=6.0 Hz, 4H), 7.03 (t, J1=6.0 Hz, J2=6.0 Hz, 2H), 6.89 (s, 1H), 6.81 (s, 1H), 3.49 (m, 4H), 3.02 (m, 2H), 1.72 (s, 3H), 1.71 (s, 3H), 1.25 (s, 3H), 1.24 (s, 3H). HRMS calcd for C42H40N2O8 701.2857 (M+H), found 701.2865. 100 mg of compound 9 was further purified using a CHIRALCEL OD-RH 5 μM 250 mm×10 mm reverse phase chiral column to give 25 mg of compound 11 and 28 mg of compound 12, respectively.

Workup

  1. waitambient temperature for 1 h
  2. stirringstirred for 30 min at room temperature
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×60 mL)
  4. washThe combined organic layer was washed with water, brine
  5. dry with materialdried over MgSO4
  6. concentrationThe solvent was concentrated in vacuo
  7. customthe residue was purified

Sources & evidence

ORD record
ord-2ad10f27efa849e797be3cbddc17e450
Source dataset
uspto-grants-2013_07
Patent number
US08487131B2

Reaction notes

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