4-tert-Butylcyclohexylamine → HCID 178497108, compound

HRID 1717693Notes

Reaction equation

HRID 1717693 reaction equation
O=[C:2]1[CH2:11][CH2:10][CH2:9][C:8]2[CH:7]=[C:6]([C:12]([O:14][CH3:15])=[O:13])[CH:5]=[CH:4][C:3]1=2.[C:16]([CH:20]1[CH2:25][CH2:24][CH:23]([NH2:26])[CH2:22][CH2:21]1)([CH3:19])([CH3:18])[CH3:17].[BH4-].[Na+]>C(O)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:16]([C@H:20]1[CH2:21][CH2:22][C@H:23]([NH:26][CH:2]2[CH2:11][CH2:10][CH2:9][C:8]3[CH:7]=[C:6]([C:12]([O:14][CH3:15])=[O:13])[CH:5]=[CH:4][C:3]2=3)[CH2:24][CH2:25]1)([CH3:19])([CH3:17])[CH3:18]

Participants

6

Reactant 3

HCID 793964-tert-ButylcyclohexylamineHCID 4311764Sodium borohydrideHCID 15309116Methyl 5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate

Product 1

HCID 178497108HCID 178497108, compound

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolvent

Procedure

A mixture of methyl 5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate (1.0 g, 4.9 mmol), titanium (IV) isopropoxide (2.8 mL, 9.8 mmol), 4-tert-butylcyclohexyl amine (1.5 g, 9.8 mmol) in absolute ethanol (75 mL) was stirred under nitrogen at room temperature for 7 h. Sodium borohydride (0.28 g, 7.4 mmol) was then added and the resulting mixture was stirred for an additional 18 h at room temperature. The reaction was quenched by pouring into aqueous ammonia (2N, 100 mL). The resulting inorganic precipitate was filtered off through Celite and washed with CH2Cl2 (100 mL). The organic layer was separated and the remaining aqueous layer was extracted once with CH2Cl2 (50 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated. Chromatography (15% EtOAc in Hexane) afforded methyl 5-[(trans-4-tert-butylcyclohexyl)amino]-5,6,7,8-tetrahydronaphthalene-2-carboxylate and the corresponding cis product (less polar). HPLC/MS: m/z=344.3 (M+1), Rt=2.84 min. 1H NMR (CDCl3): δ 7.83 (1H, d, J=8.05 Hz), 7.79 (1H, s), 7.47 (1H, d, J=8.5 Hz), 3.94 (3H, s), 2.89 (1H, m), 2.77 (1H, m), 2.62 (1H, m), 2.15 (1H, m), 2.01-1.91 (3H, m), 1.86-1.77 (4H, m), 1.56 (2H, m), 1.23-1.02 (4H, m), 0.90 (9H, s).

Workup

  1. stirringthe resulting mixture was stirred for an additional 18 h at room temperature
  2. customThe reaction was quenched
  3. additionby pouring into aqueous ammonia (2N, 100 mL)
  4. filtrationThe resulting inorganic precipitate was filtered off through Celite
  5. washwashed with CH2Cl2 (100 mL)
  6. customThe organic layer was separated
  7. extractionthe remaining aqueous layer was extracted once with CH2Cl2 (50 mL)
  8. dry with materialThe combined organic extracts were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-ce2aaa7e27b24bb0912b118a62f5e35d
Source dataset
uspto-grants-2010_09
Patent number
US07803951B2

Reaction notes

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