1-Hydroxybenzotriazole → HCID 68809822, compound

HRID 1591671Notes

Reaction equation

HRID 1591671 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[C@H:13]([C:14]([OH:16])=O)[CH2:12][C:10](=[O:11])[CH2:9]1)=[O:7])([CH3:4])[CH3:3].Cl.[F:18][C:19]1([F:23])[CH2:22][NH:21][CH2:20]1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:2]([O:5][C:6]([N:8]1[CH2:9][C:10](=[O:11])[CH2:12][C@H:13]1[C:14]([N:21]1[CH2:22][C:19]([F:23])([F:18])[CH2:20]1)=[O:16])=[O:7])([CH3:1])([CH3:3])[CH3:4]

Participants

8

Reactant 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 11593804(2S)-1-(tert-butoxycarbonyl)-4-oxopyrrolidine-2-carboxylic acid

Product 1

HCID 68809822HCID 68809822, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

N-tert-BOC-4-oxo-L-proline (458 mg, 2 mmol), 3,3-difluoroazetidine hydrochloride (258 mg, 2 mmol) (prepared as described in WO 2000/47582), and DIPEA (0.35 mL, 2 mmol) were mixed in anhydrous methylene chloride (10 mL) and cooled to 0° C. HOBT (405 mg, 3 mmol) was then added in one portion followed by EDC hydrochloride (422 mg, 2.2 mmol). The resulting mixture was allowed to warm to RT and stirred overnight. Saturated sodium bicarbonate was added, the organic layer was separated, and the aqueous phase extracted with methylene chloride. The combined organic extracts were washed twice with brine, dried over magnesium sulfate, filtered, and concentrated. The crude product (570 mg) was triturated with hexanes:methylene chloride (10:1), filtered, and dried in a vacuum oven to afford 510 mg (84% yield) of the title product as a light orange powder. MS (m/z): 305.1 (MH+).

Workup

  1. temperatureto warm to RT
  2. customthe organic layer was separated
  3. extractionthe aqueous phase extracted with methylene chloride
  4. washThe combined organic extracts were washed twice with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product (570 mg) was triturated with hexanes:methylene chloride (10:1)
  9. filtrationfiltered
  10. customdried in a vacuum oven

Sources & evidence

ORD record
ord-8baee10de3c240dcbf3e6790d5795fa9
Source dataset
uspto-grants-2007_11
Patent number
US07291618B2

Reaction notes

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