Ethanaminium, N,N,N-triethyl-, fluoride (1:1) → (3R)-3-((S)-1-(3-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-1-(methylamino)propan-2-yl)piperidine-1-carboxamide

HRID 2355491Notes

Reaction equation

HRID 2355491 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@:8]([C@@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:22]([NH:24][CH:25]([CH2:38][C:39]3([OH:45])[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]3)[CH2:26][N:27](C)[C:28](OCC[Si](C)(C)C)=O)=[O:23])[CH2:17]2)([OH:15])[CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH3:14])[CH:5]=[CH:6][CH:7]=1.[N+](CC)(CC)(CC)CC.[F-]>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C@:8]([C@@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:22]([NH:24][CH:25]([CH2:38][C:39]3([OH:45])[CH2:40][CH2:41][CH2:42][CH2:43][CH2:44]3)[CH2:26][NH:27][CH3:28])=[O:23])[CH2:17]2)([OH:15])[CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH3:14])[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 69582Ethanaminium, N,N,N-triethyl-, fluoride (1:1)HCID 67189295(3R)-3-((S)-1-(3-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)piperidine-1-carboxamide

Product 1

HCID 57544752(3R)-3-((S)-1-(3-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-1-(methylamino)propan-2-yl)piperidine-1-carboxamideYield 68.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of (3R)-3-((S)-1-(3-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)-piperidine-1-carboxamide (17.8 mg, mmol) in anhydrous THF (1 mL) was added Et4NF (3 mg). The solution was stirred at 45° C. for 2 h and evaporated under reduced pressure. The residue was purified by prep HPLC to give (3R)-3-((S)-1-(3-fluorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-1-(methylamino)propan-2-yl)piperidine-1-carboxamide (9.5 mg, 58%) as a TFA salt. 1H NMR (400 MHz, CD3OD) δ 7.32 (q, 1H), 7.16 (m, 1H), 7.14 (m. 1H), 6.94 (m, 1H), 4.42 and 4.28 (two isomers in a 3:2 ratio, d, 1H), 4.15 (m, 1H), 3.95 and 3.84 (two isomers on 3 to 2 ratio, d, 1H), 3.32 (m, 1H), 3.26 (s, 3H), 3.14 (dd, 1H), 2.95 (m, 1H), 2.70 (s, 3H), 2.60-2.39 (m 3H), 1.94 (t, 2H), 1.79-1.22 (m, 20H), 1.00 (m, 1H); MS m/z 508 (M+H+).

Workup

  1. customevaporated under reduced pressure
  2. customThe residue was purified by prep HPLC

Sources & evidence

ORD record
ord-e3dd6689b9594e3494d1028cdd5d4f8c
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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