tert-Butyl 4-formylpiperidine-1-carboxylate → HCID 68385337, compound

HRID 529332Notes

Reaction equation

HRID 529332 reaction equation
Cl.[F:2][C:3]1[C:4]([O:13][CH3:14])=[C:5]([C@@H:9]2[CH2:11][C@H:10]2[NH2:12])[CH:6]=[CH:7][CH:8]=1.[CH:15]([CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.CO.C(Cl)Cl>[F:2][C:3]1[C:4]([O:13][CH3:14])=[C:5]([C@@H:9]2[CH2:11][C@H:10]2[NH:12][CH2:15][CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[CH2:19][CH2:18]2)[CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 3

HCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 68385469HCID 68385469, compound

Product 1

HCID 68385337HCID 68385337, compoundYield 25%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of trans-2-(3-fluoro-2-methoxyphenyl)cyclopropanamine hydrochloride (Biochemistry 2010, 49(30), 6494) (500 mg, 2.76 mmol) in a mixture of 1,2-dichloroethane (20 mL) and MeOH (5 mL) was added tert-butyl 4-formylpiperidine-1-carboxylate (588 mg, 2.76 mmol) and stirred for 3 min then Na(OAc)3BH (1.75 g, 8.28 mmol) was added and stirred for 10 min at RT. The reaction mixture was diluted with DCM (100 mL) and washed with water (2×50 mL), and brine (20 mL). The organic layer was dried over anhydrous sodium sulphate and concentrated. The crude was purified by column chromatography using silica gel, eluting with 2% MeOH in DCM to afford tert-butyl 4-(((trans)-2-(3-fluoro-2-methoxyphenyl)cyclopropylamino)methyl)piperidine-1-carboxylate (250 mg, 25% yield) as yellow liquid. LCMS (ES) m/e 379.45 (M+H)+. To a solution of tert-butyl 4-(((trans)-2-(3-fluoro-2-methoxyphenyl)cyclopropylamino)methyl)piperidine-1-carboxylate (200 mg, 0.529 mmol) in 1,4-dioxane (5 mL) was added 4N HCl in 1,4-dioxane (30 mL) and stirred for 8 h at RT. The reaction mixture was concentrated and the residue was triturated with diethyl ether (50 mL), EtOAc (20 mL) and dried under high vacuum to afford (trans)-2-(3-fluoro-2-methoxyphenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine hydrochloride (130 mg, 88%) as off white solid. LCMS (ES) m/e 279.45 (M+H)+, 95.34%, (DMSO-d6) δ ppm 9.53 (bs, 2H), 8.88 (bs, 1H), 8.69 (bs, 1H), 7.15 (t, J=8.4 Hz, 1H), 7.09-7.07 (m, 1H), 6.78 (d, J=8.0 Hz, 1H), 3.90 (s, 3H), 3.29 (d, 2H), 3.0 (bs, 3H), 2.79-2.89 (m, 3H), 2.05 (bs, 1H), 1.96 (d, J=13.6 Hz, 2H), 1.63 (m, 1H), 1.38-1.47 (m, 2H), 1.24-1.29 (m, 1H).

Workup

  1. stirringstirred for 10 min at RT
  2. washwashed with water (2×50 mL), and brine (20 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  4. concentrationconcentrated
  5. customThe crude was purified by column chromatography
  6. washeluting with 2% MeOH in DCM

Sources & evidence

ORD record
ord-2f870731ed534f619ff6e359dad4478d
Source dataset
uspto-grants-2016_05
Patent number
US09346840B2

Reaction notes

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