tert-Butanol → [6-(5-tert-Butoxycarbonylamino-thiazol-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester

HRID 1798287Notes

Reaction equation

HRID 1798287 reaction equation
[CH2:1]([O:3][C:4]([CH2:6][CH:7]1[O:11][B:10]([OH:12])[C:9]2[CH:13]=[C:14]([O:18][C:19]3[S:20][C:21](C(O)=O)=[CH:22][N:23]=3)[CH:15]=[C:16]([CH3:17])[C:8]1=2)=[O:5])[CH3:2].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:34])C=CC=CC=1.C([N:46]([CH2:49]C)CC)C.[CH3:51][C:52]([OH:55])([CH3:54])[CH3:53]>>[CH2:1]([O:3][C:4](=[O:5])[CH2:6][CH:7]1[O:11][B:10]([OH:12])[C:9]2[CH:13]=[C:14]([O:18][C:19]3[S:20][C:21]([NH:46][C:49]([O:55][C:52]([CH3:54])([CH3:53])[CH3:51])=[O:34])=[CH:22][N:23]=3)[CH:15]=[C:16]([CH3:17])[C:8]1=2)[CH3:2]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 582928242-(3-Ethoxycarbonylmethyl-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-6-yloxy)-thiazole-5-carboxylic acid

Product 1

HCID 58292561[6-(5-tert-Butoxycarbonylamino-thiazol-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl esterYield 45%

Conditions

Temperature
95 °C

Procedure

To a solution of 2-(3-ethoxycarbonylmethyl-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-6-yloxy)-thiazole-5-carboxylic acid (500 mg, 1.33 mmol) in tBuOH (10 mL) was added diphenylphosphoryl azide (0.35 mL, 1.61 mmol) and triethylamine (0.41 mL, 2.95 mmol), the reaction mixture was heated to 95° C. for 1 h. The solvent was removed under vacuum and the residue was extracted with ethyl acetate. The organic portion was washed with water and brine, and dried over Na2SO4 and concentrated. The residue was purified by column chromatography (silica, DCM/MeOH=20:1) affording the title compound (270 mg, 45%) as a white solid. 1H NMR (CDCl3) δ 7.35 (s, 1H), 7.10 (s, 1H), 6.79 (s, 1H), 5.61 (dd, 1H), 4.17 (q, 2H), 3.02 (dd, 1H), 2.37 (m, 1H), 2.30 (s, 3H), 1.48 (s, 9H), 1.23 (t, 3H).

Workup

  1. customThe solvent was removed under vacuum
  2. extractionthe residue was extracted with ethyl acetate
  3. washThe organic portion was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (silica, DCM/MeOH=20:1)

Sources & evidence

ORD record
ord-4e60926bc7d4432da1bd4db90c91d0cb
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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