Water → {4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-fluorophenyl)ethyl]thio}-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetic acid

HRID 1176080Notes

Reaction equation

HRID 1176080 reaction equation
[Si:1]([O:8][C@H:9]([C:43]1[CH:48]=[CH:47][C:46]([F:49])=[CH:45][CH:44]=1)[CH2:10][S:11][C@H:12]1[C:15](=[O:16])[N:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]#[C:24][CH2:25][NH:26][S:27]([CH3:30])(=[O:29])=[O:28])=[CH:19][CH:18]=2)[C@@H:13]1[C:31]1[CH:42]=[CH:41][C:34]([O:35][CH2:36][C:37]([O:39]C)=[O:38])=[CH:33][CH:32]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].O.CCN(CC)CC.[Li+].[Cl-]>CC#N>[Si:1]([O:8][C@H:9]([C:43]1[CH:48]=[CH:47][C:46]([F:49])=[CH:45][CH:44]=1)[CH2:10][S:11][C@H:12]1[C:15](=[O:16])[N:14]([C:17]2[CH:18]=[CH:19][C:20]([C:23]#[C:24][CH2:25][NH:26][S:27]([CH3:30])(=[O:29])=[O:28])=[CH:21][CH:22]=2)[C@@H:13]1[C:31]1[CH:32]=[CH:33][C:34]([O:35][CH2:36][C:37]([OH:39])=[O:38])=[CH:41][CH:42]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 433294Lithium ChlorideHCID 86628622Methyl {4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-fluorophenyl)ethyl]thio}-1-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetate

Product 1

HCID 68774413{4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-fluorophenyl)ethyl]thio}-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetic acid

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
35 °C

Procedure

Methyl {4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-fluorophenyl)ethyl]thio}-1-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetate (530 mg, 0.73 mmol) was dissolved in 15 ml MeCN. Water (0.2 ml), Et3N (1.0 ml, 7.2 mmol) and LiCl (630 mg, 14.9 mmol) were added and the mixture was stirred at 35° C. over night. The mixture was filtered and concentrated. The residue was extracted between EtOAc and 0.3 M KHSO4. The aqueous phase was extracted with EtOAc and the combined organic phases were washed with brine (2×) and concentrated. The brown residue was purified by preparative HPLC on a C8 column (150×30 mm) using a gradient from 20-60% MeCN in 0.1 M ammonium acetate as eluent. The title compound was obtained in 170 mg (33%) as a slightly brownish solid. M/z: 711.2 (M−1). 1H-NMR (400 MHz, DMSO-d6) δ: −0.18 (s, 3H), −0.04 (s, 3H), 0.78 (s, 9H), 2.93 (ddd, 2H), 2.98 (s, 3H), 4.01 (d, 2H), 4.29 (d, 1H), 4.67 (s, 2H), 4.88-4.94 (m, 1H), 5.11 (d, 1H), 6.93 (d, 2H), 7.09-7.18 (m, 2H), 7.21 (d, 2H), 7.32-7.42 (m, 6H), 7.58 (t, 1H), 12.97 (brs, 1H).

Workup

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated
  3. extractionThe residue was extracted between EtOAc and 0.3 M KHSO4
  4. extractionThe aqueous phase was extracted with EtOAc
  5. washthe combined organic phases were washed with brine (2×)
  6. concentrationconcentrated
  7. customThe brown residue was purified by preparative HPLC on a C8 column (150×30 mm)

Sources & evidence

ORD record
ord-185a7a5a742b4578b08c9bd28c766f56
Source dataset
uspto-grants-2010_11
Patent number
US07842684B2

Reaction notes

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