3-Hydroxyazetidine hydrochloride → HCID 178480268, compound

HRID 2064503Notes

Reaction equation

HRID 2064503 reaction equation
[C:1]([C:5]1[N:9]([CH3:10])[N:8]([CH2:11][CH:12]2[CH2:14][CH2:13]2)/[C:7](=[N:15]/[C:16](=[O:29])[C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:18]=2[CH:27]=[O:28])/[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[NH:31]1[CH2:34][CH:33]([OH:35])[CH2:32]1.C([BH3-])#N.[Na+]>>[C:27]([O-:28])(=[O:35])[CH3:18].[NH4+:8].[C:1]([C:5]1[N:9]([CH3:10])[N:8]([CH2:11][CH:12]2[CH2:13][CH2:14]2)/[C:7](=[N:15]/[C:16](=[O:29])[C:17]2[CH:22]=[C:21]([C:23]([F:25])([F:26])[F:24])[CH:20]=[CH:19][C:18]=2[CH2:27][N:31]2[CH2:34][CH:33]([OH:35])[CH2:32]2)/[CH:6]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 27592903-Hydroxyazetidine hydrochlorideHCID 5003444Sodium cyanoborohydrideHCID 178480269HCID 178480269, compound

Product 2

HCID 517165Ammonium AcetateHCID 178480268HCID 178480268, compoundYield 65.2%

Procedure

To a mixture of Example 9H (100 mg, 0.245 mmol) and azetidin-3-ol hydrochloride (53.8 mg, 0.491 mmol) in pH 4 buffer solution (4 mL) (acetic acid and sodium acetate in MeOH) was added sodium cyanoborohydride (31 mg, 0.49 mmol) portion wise. The mixture was stirred at ambient temperature for 2 hours then concentrated under reduced pressure. The residue was dissolved in EtOAc and washed with saturated aqueous NaHCO3 and brine. The organic extract was dried over MgSO4, filtered, and concentrated under reduced pressure. Purification of the residue by HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile:10 mM ammonium acetate over 8 min (10 min run time) at a flow rate of 40 mL/min to afford 37.1 mg (32.5%) of the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 0.49-0.68 (m, 4H), 1.05-1.19 (m, 1H), 1.48 (s, 9H), 3.94 (s, 3H), 4.02-4.12 (m, 2H), 4.12-4.22 (m, 2H), 4.29 (d, J=7.12 Hz, 2H), 4.49-4.59 (m, 1H), 4.70 (s, 2H), 5.07 (s, 1H), 6.93 (s, 1H), 7.64-7.69 (m, 2H), 8.33 (s, 1H); MS (ESI) m/z 465 [M+H]+, 463[M−H]−.

Workup

  1. concentrationthen concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in EtOAc
  3. washwashed with saturated aqueous NaHCO3 and brine
  4. extractionThe organic extract
  5. dry with materialwas dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification of the residue by HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size)

Sources & evidence

ORD record
ord-3d5455314b624d0cbce313e55ecd2122
Source dataset
uspto-grants-2012_10
Patent number
US08288428B2

Reaction notes

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