Sodium Bicarbonate → HCID 71152377, compound

HRID 1497295Notes

Reaction equation

HRID 1497295 reaction equation
[F:1][CH:2]([F:16])[C@@H:3]1[C@@H:13]([OH:14])[C@H:12]([OH:15])[C@H:6]2[N:7]=[C:8](SC)[O:9][C@H:5]2[CH2:4]1.Cl.[NH:18]1[CH2:21][CH2:20][CH2:19]1.C([O-])(O)=O.[Na+]>CCO>[N:18]1([C:8]2[O:9][C@H:5]3[CH2:4][C@H:3]([CH:2]([F:16])[F:1])[C@@H:13]([OH:14])[C@H:12]([OH:15])[C@H:6]3[N:7]=2)[CH2:21][CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 12308726Azetidine hydrochlorideHCID 71152509HCID 71152509, compound

Product 1

HCID 71152377HCID 71152377, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of (3 aR,4R,5R,6S,7aS)-6-(difluoromethyl)-2-(methylthio)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazole-4,5-diol (52.6 mg, 0.208 mmol) in EtOH (5 mL) was added azetidine hydrochloride (97 mg, 1.04 mmol). The mixture was heated at reflux for 5 h. After cooling, solid NaHCO3 (200 mg, 2.38 mmol) was added and stirred for 10 min Solvent was evaporated and the residue was purified by silica gel column chromatography, eluted with 5% 2 M NH3 MeOH solution in DCM to give the product (3aR,4R,5R,6S,7aS)-2-(azetidin-1-yl)-6-(difluoromethyl)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazole-4,5-diol (46.2 mg, 85%) as a white solid. MS m/z 263.1 (M+1, 100%); 1H NMR (400 MHz, MeOD) δ 6.14 (td, J=56.8 Hz, 1.8 Hz, 1H), 4.66-4.69 (m, 1H), 4.00 (t, J=7.6 Hz, 4H), 3.62 (t, J=7.2 Hz, 1H), 3.34 (t, J=9.2 Hz, 1H), 3.24 (t, J=7.9 Hz, 1H), 2.29-2.36 (m, 2H), 2.21 (dt, J=15.1 Hz, 3.6 Hz, 1H), 1.95-2.10 (m, 1H), 1.82-1.90 (m, 1H); 13C NMR (100 MHz, MeOD) δ 164.62, 117.96 (t, J=238.5 Hz), 81.20, 79.89 (d, J=1.6 Hz), 71.36 (dd, J=7.2 Hz, 1.0 Hz), 68.72, 51.91, 42.25 (t, J=19.8 Hz), 22.61 (t, J=4.7 Hz), 17.75.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 5 h
  3. temperatureAfter cooling
  4. customwas evaporated
  5. customthe residue was purified by silica gel column chromatography
  6. washeluted with 5% 2 M NH3 MeOH solution in DCM

Sources & evidence

ORD record
ord-f139348dd12a4adaa1b1d894a69abe73
Source dataset
uspto-grants-2015_12
Patent number
US09199949B2

Reaction notes

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