4-tert-Butylcyclohexylamine → HCID 178450643, compound

HRID 1717691Notes

Reaction equation

HRID 1717691 reaction equation
O=[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([O:13][CH2:14][CH2:15][CH2:16][CH3:17])=[O:12])=[CH:8][CH:9]=2)[CH2:4][CH2:3]1.[C:18]([CH:22]1[CH2:27][CH2:26][CH:25]([NH2:28])[CH2:24][CH2:23]1)([CH3:21])([CH3:20])[CH3:19].[BH4-].[Na+]>C(O)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:18]([C@H:22]1[CH2:23][CH2:24][C@H:25]([NH:28][CH:2]2[C:10]3[C:5](=[CH:6][C:7]([C:11]([O:13][CH2:14][CH2:15][CH2:16][CH3:17])=[O:12])=[CH:8][CH:9]=3)[CH2:4][CH2:3]2)[CH2:26][CH2:27]1)([CH3:21])([CH3:19])[CH3:20]

Participants

6

Reactant 3

HCID 793964-tert-ButylcyclohexylamineHCID 4311764Sodium borohydrideHCID 67484921Butyl 1-oxoindane-5-carboxylate

Product 1

HCID 178450643HCID 178450643, compound

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolvent

Procedure

A mixture of butyl 1-oxoindane-5-carboxylate (5.0 g, 21.5 mmol), titanium (IV) isopropoxide (7.04 mL, 23.7 mmol), 4-tert-butylcyclohexyl amine (6.68 g, 43.0 mmol) in absolute ethanol (60 mL) was stirred under nitrogen at room temperature for 18 h. Sodium borohydride (1.22 g, 32.2 mmol) was then added and the resulting mixture was stirred for an additional 24 h at room temperature. The reaction was quenched by pouring into aqueous ammonia (2N, 200 mL). The resulting inorganic precipitate was filtered off through Celite and washed with CH2Cl2 (300 mL). The organic layer was separated and the remaining aqueous layer was extracted once with CH2Cl2 (150 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated. Chromatography (8% to 15% EtOAc in Hexane) afforded butyl 1-[(trans-4-tert-butylcyclohexyl)amino]indane-5-carboxylate and the corresponding cis product (less polar than the trans amine). HPLC/MS: m/z=372.3 (M+1), Rt=2.14 min. 1H NMR (CDCl3): δ 7.93 (1H, d, J=8.0 Hz), 7.92 (1H, s), 7.43 (1H, d, J=8.0 Hz), 4.41 (1H, t, J=6.5 Hz), 4.35 (2H, t, J=6.5 Hz), 3.05 (1H, ddd, J=4.0 Hz, 8.0 Hz, 16.0 Hz), 2.86 (1H, dt, J=8.0 Hz, 16.0 Hz), 2.65 (1H, m), 2.51 (1H, m), 2.10 (1H, m), 2.02 (1H, m), 1.88-1.76 (5H, m), 1.56-1.48 (2H, m), 1.22-1.01 (8H, m), 0.90 (9H, s).

Workup

  1. stirringthe resulting mixture was stirred for an additional 24 h at room temperature
  2. customThe reaction was quenched
  3. additionby pouring into aqueous ammonia (2N, 200 mL)
  4. filtrationThe resulting inorganic precipitate was filtered off through Celite
  5. washwashed with CH2Cl2 (300 mL)
  6. customThe organic layer was separated
  7. extractionthe remaining aqueous layer was extracted once with CH2Cl2 (150 mL)
  8. dry with materialThe combined organic extracts were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-b71045449e434550875a2397bda83bf2
Source dataset
uspto-grants-2010_09
Patent number
US07803951B2

Reaction notes

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