Sodium Bicarbonate → HCID 71152229, compound

HRID 1497302Notes

Reaction equation

HRID 1497302 reaction equation
[F:1][C@H:2]1[C@H:7]2[N:8]=[C:9](SC)[O:10][C@H:6]2[CH2:5][C@H:4]([CH2:13][OH:14])[C@H:3]1[OH:15].Cl.[NH:17]1[CH2:20][CH2:19][CH2:18]1.C([O-])(O)=O.[Na+]>CCO>[N:17]1([C:9]2[O:10][C@H:6]3[CH2:5][C@H:4]([CH2:13][OH:14])[C@@H:3]([OH:15])[C@@H:2]([F:1])[C@H:7]3[N:8]=2)[CH2:20][CH2:19][CH2:18]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 12308726Azetidine hydrochlorideHCID 71152272HCID 71152272, compound

Product 1

HCID 71152229HCID 71152229, compoundYield 61.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of (3 aS,4S,5R,6R,7aS)-4-fluoro-6-(hydroxymethyl)-2-(methylthio)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazol-5-ol (50 mg, 0.21 mmol) in EtOH (3 mL) was added azetidine hydrochloride (100 mg, 1.06 mmol). The mixture was heated at reflux for 17 h. After cooling, solid NaHCO3 (100 mg, 1.19 mmol) was added and stirred for 10 min. Solvent was evaporated and the residue was purified by silica gel column chromatography, eluted with 5%-10% 2 M NH3 MeOH solution in DCM to give the product (3aS,4S,5R,6R,7aS)-2-(azetidin-1-yl)-4-fluoro-6-(hydroxymethyl)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazol-5-ol (31.4 mg, 60%) as a white solid. MS m/z 245.1 (M+1, 100%); 1H NMR (400 MHz, MeOD) δ 4.57-4.61 (m, 1H), 4.58 (ddd, J=52.8 Hz, 3.7 Hz, 1.6 Hz, 1H), 4.02 (t, J=7.6 Hz, 4H), 3.85 (ddd, J=26.1 Hz, 7.1 Hz, 3.8 Hz, 1H), 3.66-3.73 (m, 2H), 3.49 (ddd, J=30.2 Hz, 10.0 Hz, 1.5 Hz, 1H), 2.27-2.38 (m, 3H), 2.01-2.09 (m, 1H), 1.73-1.81 (m, 1H); 13C NMR (100 MHz, MeOD) δ 165.85, 93.17 (d, J=178.6 Hz), 80.71, 70.65 (d, J=19.1 Hz), 64.45 (d, J=17.3 Hz), 63.94, 51.87, 35.47 (d, J=5.8 Hz), 28.39, 17.77.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 17 h
  3. temperatureAfter cooling
  4. customSolvent was evaporated
  5. customthe residue was purified by silica gel column chromatography
  6. washeluted with 5%-10% 2 M NH3 MeOH solution in DCM

Sources & evidence

ORD record
ord-0ef9e3b6a8ab4593a05537d164848a91
Source dataset
uspto-grants-2015_12
Patent number
US09199949B2

Reaction notes

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