Methyl 6-(adamantan-1-ylmethoxy)-5-chloronicotinate → Methyl 5-cyclopropyl-2-fluoro-4-((3,5,7-trifluoroadamantan-1-yl)methoxy)benzoate

HRID 1849700Notes

Reaction equation

HRID 1849700 reaction equation
[C:1]12([CH2:11]OC3C(Cl)=CC(C(OC)=O)=CN=3)CC3CC(CC(C3)[CH2:2]1)C2.Cl[C:25]1[C:26]([O:36][CH2:37][C:38]23[CH2:48][C:42]4([F:49])[CH2:43][C:44]([F:47])([CH2:46][C:40]([F:50])([CH2:41]4)[CH2:39]2)[CH2:45]3)=[CH:27][C:28]([F:35])=[C:29]([CH:34]=1)[C:30]([O:32][CH3:33])=[O:31]>>[CH:11]1([C:25]2[C:26]([O:36][CH2:37][C:38]34[CH2:45][C:44]5([F:47])[CH2:43][C:42]([F:49])([CH2:41][C:40]([F:50])([CH2:46]5)[CH2:39]3)[CH2:48]4)=[CH:27][C:28]([F:35])=[C:29]([CH:34]=2)[C:30]([O:32][CH3:33])=[O:31])[CH2:1][CH2:2]1

Participants

3

Reactant 2

HCID 86702922Methyl 6-(adamantan-1-ylmethoxy)-5-chloronicotinateHCID 86703571Methyl 5-chloro-2-fluoro-4-((3,5,7-trifluoroadamantan-1-yl)methoxy)benzoate

Product 1

HCID 86703572Methyl 5-cyclopropyl-2-fluoro-4-((3,5,7-trifluoroadamantan-1-yl)methoxy)benzoateYield 62%

Procedure

Following the procedure as described in Example 150 step 3 and making variations as required to replace methyl 6-(adamantan-1-ylmethoxy)-5-chloronicotinate with methyl 5-chloro-2-fluoro-4-((3,5,7-trifluoroadamantan-1-yl)methoxy)benzoate. Purification by silica gel column chromatography (10:1 hexanes:ethyl acetate) gave the title compound as a colorless solid (0.57 g, 62%): 1H NMR (300 MHz, CDCl3) 7.49 (d, J=8.2 Hz, 1H), 6.51 (d, J=12.6 Hz, 1H), 3.87 (s, 3H), 3.81 (s, 2H), 2.24-2.14 (m, 3H), 2.14-2.04 (m, 3H), 1.99-1.88 (m, 1H), 1.86-1.79 (m, 6H), 0.96-0.88 (m, 2H), 0.66-0.58 (m, 2H); MS (ES+) m/z 413.2 (M+1).

Workup

  1. customPurification by silica gel column chromatography (10:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-6d3daf28c90b4b77be25270cf14b2de7
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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