Triethylamine → (S)-[1-(6-Fluoropyridin-3-yl)-pyrrolidin-3-yl]-(4-trifluoromethylbenzyl)-amine

HRID 252108Notes

Reaction equation

HRID 252108 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1.Cl.[F:14][C:15]1[N:20]=[CH:19][C:18]([N:21]2[CH2:25][CH2:24][CH:23]([NH2:26])[CH2:22]2)=[CH:17][CH:16]=1.C(N(CC)CC)C.[BH4-].[Na+]>CO>[F:14][C:15]1[N:20]=[CH:19][C:18]([N:21]2[CH2:25][CH2:24][C@H:23]([NH:26][CH2:7][C:6]3[CH:9]=[CH:10][C:3]([C:2]([F:12])([F:11])[F:1])=[CH:4][CH:5]=3)[CH2:22]2)=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 679964-(Trifluoromethyl)benzaldehydeHCID 4311764Sodium borohydrideHCID 668545511-(6-Fluoropyridin-3-yl)-pyrrolidin-3-ylamine hydrochloride

Product 1

HCID 59860372(S)-[1-(6-Fluoropyridin-3-yl)-pyrrolidin-3-yl]-(4-trifluoromethylbenzyl)-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Add 4-(trifluoromethyl)benzaldehyde (30 μL, 0.22 mmol) to a solution of 1-(6-fluoropyridin-3-yl)-pyrrolidin-3-ylamine hydrochloride (43 mg, 0.2 mmol) and triethylamine (90 μL, 0.66 mmol) in methanol (1 mL). Vortex the resulting mixture and allow to sit for 18 h. Add sodium borohydride (12-15 mg, 0.3-0.4 mmol). When the bubbling begins to subside, vortex and allow to sit for 1 h. Dilute the reaction mixture with methanol (2 mL) and pour onto a column of Dowex® 50Wx2 (H+ form). Rinse the column with methanol, elute the product with 5% triethylamine in methanol and concentrate. Redissolve the residue in methanol, dilute with acetonitrile and concentrate to dryness to give the title compound as a residue.

Workup

  1. waitto sit for 1 h
  2. additionpour onto a column of Dowex® 50Wx2 (H+ form)
  3. washRinse the column with methanol
  4. washelute the product with 5% triethylamine in methanol
  5. concentrationconcentrate
  6. dissolutionRedissolve the residue in methanol
  7. additiondilute with acetonitrile
  8. concentrationconcentrate to dryness

Sources & evidence

ORD record
ord-49a4b9e2046a4f0b9c9d5b663f1608e9
Source dataset
uspto-grants-2011_01
Patent number
US07868014B2

Reaction notes

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