4-Methylmorpholine → N-[(4-{(2R,3R)-4-oxo-3-[(2-oxo-2-phenylethyl)thio]-1-phenylazetidin-2-yl}phenoxy)acetyl]glycine

HRID 254069Notes

Reaction equation

HRID 254069 reaction equation
C([O:5][C:6](=[O:9])[CH2:7][NH2:8])(C)(C)C.CN1CC[O:14][CH2:13][CH2:12]1.CC1(C)CO[C:21]([CH2:30][S:31][C@H:32]2[C:35](=[O:36])[N:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[C@@H:33]2[C:43]2[CH:53]=[CH:52][C:46]([O:47]CC(O)=O)=[CH:45][CH:44]=2)([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[O:20]C1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl>[O:36]=[C:35]1[N:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C@H:33]([C:43]2[CH:53]=[CH:52][C:46]([O:47][CH2:12][C:13]([NH:8][CH2:7][C:6]([OH:5])=[O:9])=[O:14])=[CH:45][CH:44]=2)[C@H:32]1[S:31][CH2:30][C:21](=[O:20])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 151417Glycine tert-butyl esterHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66842903[4-((2R,3R)-3-([(5,5-dimethyl-2-phenyl-1,3-dioxan-2-yl)methyl]thio}-4-oxo-1-phenylazetidin-2-yl)phenoxy]acetic acid

Product 1

HCID 66842612N-[(4-{(2R,3R)-4-oxo-3-[(2-oxo-2-phenylethyl)thio]-1-phenylazetidin-2-yl}phenoxy)acetyl]glycine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Glycine tert-butyl ester (0.015 g, 0.112 mmol) and N-Methylmorpholine (0.028 g, 0.281 mmol) were added to a solution of [4-((2R,3R)-3-{[(5,5-dimethyl-2-phenyl-1,3-dioxan-2-yl)methyl]thio}-4-oxo-1-phenylazetidin-2-yl)phenoxy]acetic acid (0.050 g, 0.094 mmol) in CH2Cl2 (5 ml). After 10 minutes, TBTU (0.039 g, 0.122 mmol) was added. The reaction was stirred overnight. The resulting tert-butyl ester was purified on silica gel and eluted with EtOAc/CH2Cl2 (25/75). The pure fractions were collected and concentrated. CH2Cl2 (4 ml) and TFA (1 ml) were added. The solvent was evaporated after 2 h and the residue was purified by preparative HPLC using an eluent of 20-70% CH3CN in 0.1M NH4OAc buffer. Freeze-drying of the pure fractions gave the title product as a colourless solid. M/z: 503.5 (M-1). 1H NMR (CD3CN), 400 MHz] δ 3.84 (d, 2H), 4.18 (d, 1H), 4.24 (s, 2H), 4.50 (s, 2H), 5.04 (d, 1H), 6.99-7.12 (m, 3H), 7.25-7.66 (m, 9H), 7.94-7.96 (m, 2H).

Workup

  1. customThe resulting tert-butyl ester was purified on silica gel
  2. washeluted with EtOAc/CH2Cl2 (25/75)
  3. customThe pure fractions were collected
  4. concentrationconcentrated
  5. additionCH2Cl2 (4 ml) and TFA (1 ml) were added
  6. customThe solvent was evaporated after 2 h
  7. customthe residue was purified by preparative HPLC
  8. customFreeze-drying of the pure fractions

Sources & evidence

ORD record
ord-189c148cfda34a7cbac993983fec7993
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

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