Azetidine → HCID 86643245, compound

HRID 2387937Notes

Reaction equation

HRID 2387937 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]([N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([CH:15]=O)[CH:11]=2)[CH2:6]1)=[O:4].[NH:19]1[CH2:22][CH2:21][CH2:20]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>ClCCCl>[N:19]1([CH2:15][C:10]2[CH:11]=[C:12]3[C:7](=[CH:8][CH:9]=2)[CH2:6][N:5]([C:3](=[O:4])[C:2]([F:18])([F:17])[F:1])[CH2:14][CH2:13]3)[CH2:22][CH2:21][CH2:20]1

Participants

6

Reactant 4

HCID 10422AzetidineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 75176179HCID 75176179, compound

Product 1

HCID 86643245HCID 86643245, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
25 °C

Procedure

2-(2,2,2-Trifluoro-acetyl)-1,2,3,4-tetrahydro-isoquinoline-6-carbaldehyde (7.776 mmol, 1 equiv.) and azetidine (9.331 mmol, 1.2 equiv.) were dissolved in 1,2-dichloroethane (37 ml), and the mixture was stirred for 10 minutes at 25° C. Sodium triacetoxyborohydride (10.89 mmol, 1.4 equiv.) was added, and the reaction mixture was stirred for 16 hours at 25° C. Saturated sodium hydrogen carbonate solution (50 ml) was then added, the phases were separated, and the aqueous phase was extracted with dichloromethane (4×20 ml). The combined organic phases were washed with saturated NaCl solution (1×50 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (ethyl acetate/dichloromethane/hexane/methanol/-ammonia (25% aq), 30:10:10:2:0.02). Yield: 1.55 g (67%)

Workup

  1. stirringthe reaction mixture was stirred for 16 hours at 25° C
  2. customthe phases were separated
  3. extractionthe aqueous phase was extracted with dichloromethane (4×20 ml)
  4. washThe combined organic phases were washed with saturated NaCl solution (1×50 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography (ethyl acetate/dichloromethane/hexane/methanol/-ammonia (25% aq), 30:10:10:2:0.02)

Sources & evidence

ORD record
ord-f51a5f0698bf4ef8b2b21130cccdb3d9
Source dataset
uspto-grants-2012_09
Patent number
US08269000B2

Reaction notes

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