1-Adamantanecarbonyl chloride → HCID 10660816, compound

HRID 234648Notes

Reaction equation

HRID 234648 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C@H:7]([OH:9])[CH3:8])[CH:2]=1.C([Li])CCC.[C:15]12([C:25](Cl)=[O:26])[CH2:24][CH:19]3[CH2:20][CH:21]([CH2:23][CH:17]([CH2:18]3)[CH2:16]1)[CH2:22]2>C1COCC1.CCCCCC>[C:15]12([C:25]([O:9][C@@H:7]([C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)[CH3:8])=[O:26])[CH2:22][CH:21]3[CH2:20][CH:19]([CH2:18][CH:17]([CH2:23]3)[CH2:16]1)[CH2:24]2

Participants

6

Reactant 3

HCID 989151-Adamantanecarbonyl chlorideHCID 10796735(1R)-1-(Pyridin-3-yl)ethan-1-olHCID 178418339Butyllithium

Product 1

HCID 10660816HCID 10660816, compoundYield 81.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

The method followed that described in Example 1, but using (+)-(R)-1-(3-pyridyl)ethanol [87% ee; prepared by asymmetric reduction of 3-acetylpyridine with (+)-B-chlorodiisopinocampheyl borane, J. Chandrasekharan, P. V. Ranachandran and H. C. Brown, J. Org. Chem., 50, 5446-5448 (1985)] (0.62 g, 5.0 mmol) in THF (20 ml), n-butyllithium (2.5 M; 2.0 ml, 5.0 mmol) in hexane, and 1-adamantanecarbonyl chloride (1.09 g, 5.5 mmol) in THF (5 ml). Chromatography, on elution with ether-petrol-triethylamine 100:50:1, gave the title compound (1.16 g, 81%) as an oil. [α]D +29.9° (c 2, MeOH), 87% ee. Recrystallisation of the (-)-(1R)-10-camphorsulfonate salt from ethyl acetate, and reliberation of the free-base, afforded the title compound with 98% ee, [α]D +33.7° (c 2, MeOH). IR νmax 1728 cm-1 ; 1H-NMR (CDCl3) δ1.54 (3H, d, J 6.5 Hz, CHCH3), 1.72 and 1.90 (12H, 2s, adamantyl CH2), 2.03 (3H, s, adamantyl CH), 5.88 (1H, q, J 6.5 Hz, CHCH3), 7.30 (1H, m, Py 5-H), 7.65 (1H, m, Py 4-H), 8.56 (1H, m, Py 6-H), 8.63 (1H, m, Py 2-H); MS m/z 285 (M+). Anal. Calcd: C, 75.76; H, 8.12; N, 4.91. Found: C, 75.30; H, 8.18; N, 4.46%.

Workup

  1. washChromatography, on elution with ether-petrol-triethylamine 100:50:1

Sources & evidence

ORD record
ord-90004cd3d7c7448e99334a70f2ad59bc
Source dataset
uspto-grants-1997_01
Patent number
US05595995

Reaction notes

Loading…