Norcamphor → 1'-(bicyclo[2.2.1]heptan-2-yl)-N-methylspiro[indene-1,4'-piperidine]-3-carboxamide

HRID 2267112Notes

Reaction equation

HRID 2267112 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:7]2([CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=1)=[O:4].[C@H:19]12[CH2:25][C@H:22]([CH2:23][CH2:24]1)[CH2:21][C:20]2=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH:19]12[CH2:25][CH:22]([CH2:23][CH2:24]1)[CH2:21][CH:20]2[N:10]1[CH2:11][CH2:12][C:7]2([C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:5]([C:3]([NH:2][CH3:1])=[O:4])=[CH:6]2)[CH2:8][CH2:9]1

Participants

6

Reactant 3

HCID 449588NorcamphorHCID 5049666Sodium triacetoxyborohydrideHCID 59600609N-methylspiro[indene-1,4'-piperidine]-3-carboxamide

Product 1

HCID 596006101'-(bicyclo[2.2.1]heptan-2-yl)-N-methylspiro[indene-1,4'-piperidine]-3-carboxamide

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 63651,1-DichloroethaneSolvent

Procedure

A mixture of (C6) (0.015 g, 0.073 mmol), titanium (IV) isopropoxide (0.065 mL, 0.22 mmol) and (1R,4S)-bicyclo[2.2.1]heptan-2-one (3 eq) was stirred at room temperature for 18 h in dichloroethane (0.5 mL). Sodium triacetoxyborohydride (0.013 g, 0.073 mmol) was added and the reaction stirred at room temperature for 1 h. The solvent was evaporated and 6N NaOH (0.5 mL) and methanol (1 mL) was added and triturated to give a white solid. The solid was washed with methanol (1 mL) and EtOAc (1 mL). The filtrate was concentrated under reduced pressure to afford the crude product that was purified by reverse phase preparative HPLC to afford 1′-(bicyclo[2.2.1]heptan-2-yl)-N-methylspiro[indene-1,4′-piperidine]-3-carboxamide (Compound No. 38) (0.012 g) as an oil. LC/MS (10-90% over 3 min with 0.9% FA) m/z 337.2 (M+1), Rt 1.7 minutes. 1HNMR (500 MHz, CD3OD): δ 7.74 (d, 1H), 7.35 (m, 4H), 3.73 (m, 2H), 3.55 (m, 1H), 3.30 (m, 2H), 2.91 (s, 3H), 2.42-2.74 (m, 5H), 2.19 (m, 2H), 1.54-1.74 (m, 8H), 1.31 (m, 1H)

Workup

  1. customThe solvent was evaporated
  2. addition6N NaOH (0.5 mL) and methanol (1 mL) was added
  3. customtriturated
  4. customto give a white solid
  5. washThe solid was washed with methanol (1 mL) and EtOAc (1 mL)
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customto afford the crude product that
  8. customwas purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-1671c58fd0e844ef8089ea1db088bef2
Source dataset
uspto-grants-2010_12
Patent number
US07858790B2

Reaction notes

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