Acetic Acid → HCID 11215978, compound

HRID 2252419Notes

Reaction equation

HRID 2252419 reaction equation
C([O:4][C@H:5]([C:55]1[CH:60]=[CH:59][C:58]([F:61])=[CH:57][CH:56]=1)[CH2:6][CH2:7][C@@H:8]1[C@@H:11]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][C@H:25]4[O:42][C@@H:41]([C:43]([O:45]O)=[O:44])[C@H:36]([O:37]C(=O)C)[C@@H:31]([O:32]C(=O)C)[C@@H:26]4[O:27]C(=O)C)[CH:19]=3)=[CH:14][CH:13]=2)[N:10]([C:47]2[CH:52]=[CH:51][C:50]([F:53])=[CH:49][CH:48]=2)[C:9]1=[O:54])(=O)C.O.C(O)(=O)C.CO>CO.C(N(CC)CC)C.ClCCl>[O:24]([C:20]1[CH:19]=[C:18]([C:15]2[CH:16]=[CH:17][C:12]([C@@H:11]3[C@@H:8]([CH2:7][CH2:6][C@@H:5]([C:55]4[CH:60]=[CH:59][C:58]([F:61])=[CH:57][CH:56]=4)[OH:4])[C:9](=[O:54])[N:10]3[C:47]3[CH:48]=[CH:49][C:50]([F:53])=[CH:51][CH:52]=3)=[CH:13][CH:14]=2)[CH:23]=[CH:22][CH:21]=1)[C@H:25]1[O:42][C@@H:41]([C:43]([OH:45])=[O:44])[C@H:36]([OH:37])[C@@H:31]([OH:32])[C@@H:26]1[OH:27]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 887MethanolHCID 962WaterHCID 86600746HCID 86600746, compound

Product 1

HCID 11215978HCID 11215978, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22728368Triethylamine methanolSolvent

Procedure

The product of step 3 (57.2 mg, 0.068 mmol) was dissolved in 1:1 methanol-triethylamine (2.8 mL). To this solution was added water (4.25 mL). The reaction progress was monitored by TLC (5% acetic acid and 15% methanol in dichloromethane) and was complete after 19 hours. The methanol and triethylamine were evaporated in vacuo, the residue was acidified with 1 N aqueous hydrochloric acid (1.4 mL), extracted with ethyl acetate (20 mL), washed with brine (5 mL), dried over sodium sulfate, filtered, concentrated and purified by chromatography (10 g silica gel, 5% acetic acid and 15% methanol in dichloromethane) to afford 4′-{(2S,3R)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetidin-2-yl}biphenyl-3-yl β-L-glucopyranosiduronic acid (32.6 mg, 73%) as an off-white foam; Rf 0.37 (5% acetic acid and 15% methanol in dichloromethane); 1H NMR (300 MHz, CD3OD) δ 7.63 (d, J=7.8 Hz, 2H), 7.43 (d, J=8.1 Hz, 2H), 7.33 (m, 7H), 7.06 (m, 5H), 5.03 (m, 1H), 4.63 (t, J=5.1, 5.1 Hz, 2H), 3.94 (m, 3H), 3.13 (m, 1H) 1.91 (m, 4H) ppm; MS [M−H] 660.6.

Workup

  1. customThe methanol and triethylamine were evaporated in vacuo
  2. extractionextracted with ethyl acetate (20 mL)
  3. washwashed with brine (5 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by chromatography (10 g silica gel, 5% acetic acid and 15% methanol in dichloromethane)

Sources & evidence

ORD record
ord-f5b696c0361c40899bac5b63b0a5212d
Source dataset
uspto-grants-2008_01
Patent number
US07320972B2

Reaction notes

Loading…