Potassium Phosphate, Dibasic → Benzyl ((2R,3S)-2-((5-methyl-2H-tetrazol-2-yl)methyl)-4-oxoazetidin-3-yl)carbamate

HRID 708354Notes

Reaction equation

HRID 708354 reaction equation
COC1C=C(OC)C=CC=1C[N:6]1[C:9](=[O:10])[C@@H:8]([NH:11][C:12](=[O:21])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C@H:7]1[CH2:22][N:23]1C(C)=N[NH:25][NH:24]1.OP([O-])([O-])=O.[K+].[K+].[C:42](#[N:44])[CH3:43].O>>[CH3:43][C:42]1[N:25]=[N:24][N:23]([CH2:22][C@@H:7]2[C@H:8]([NH:11][C:12](=[O:21])[O:13][CH2:14][C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:9](=[O:10])[NH:6]2)[N:44]=1

Participants

4

Reactant 3

HCID 24450Potassium Phosphate, Dibasic2×HCID 18373917Acetonitrile--water (1/1)HCID 131733726benzyl((2R,3S)-1-(2,4-dimethoxybenzyl)-2-((5-methyl-2H-tetrazol-1-yl)methyl)-4-oxoazetidin-3-yl)carbamate

Product 1

HCID 131733725Benzyl ((2R,3S)-2-((5-methyl-2H-tetrazol-2-yl)methyl)-4-oxoazetidin-3-yl)carbamateYield 81%

Procedure

Prepared in an analogous manner to example 4, step 2 using benzyl ((2R,3S)-1-(2,4-dimethoxybenzyl)-2-((5-methyl-2H-tetrazol-1-yl)methyl)-4-oxoazetidin-3-yl)carbamate (202 mg, 0.433 mmol), K2S2O8 (164 mg, 0.606 mmol) and K2HPO4 (98 mg, 0.563 mmol) in ACN:water (2:1, 7.4 mL) at 90° C. for 1.5 h. More K2S2O8 (35 mg, 0.13 mmol) and K2HPO4 (20 mg, 0.11 mmol) were added and it was heated for an additional 30 min then cooled to rt then concentrated in vacuo. The mixture was diluted with EtOAc, washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude residue was purified via silica gel chromatography (MeOH-DCM, 0-10%), to afford the title compound (111 mg, 81%). LCMS: Rt=0.58 min, m/z=317.2 (M+1) Method 2m_acidic; 1H NMR (400 MHz, CDCl3) δ 7.43-7.30 (m, 5H), 6.34 (br s, 1H), 6.01 (br s, 1H), 5.28-5.21 (m, 1H), 5.20-5.12 (m, 3H), 4.92 (dd, J=14.3, 3.9 Hz, 1H), 4.68 (dd, J=14.2, 7.9 Hz, 1H), 4.48-4.27 (m, 2H), 2.53 (s, 3H).

Workup

  1. temperatureit was heated for an additional 30 min
  2. concentrationthen concentrated in vacuo
  3. additionThe mixture was diluted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified via silica gel chromatography (MeOH-DCM, 0-10%)

Sources & evidence

ORD record
ord-d15610d427c544a9a5205edac64208f8
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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