Diisopropylethylamine → 2-(trimethylsilyl)ethyl (2S,3S)-3-((R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-4-cyclohexyl-2-hydroxybutylcarbamate

HRID 253596Notes

Reaction equation

HRID 253596 reaction equation
[Cl:1][C:2]1[C:3]([F:22])=[C:4]([C@:8]([C@@H:16]2[CH2:21][CH2:20][CH2:19][NH:18][CH2:17]2)([OH:15])[CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH3:14])[CH:5]=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.[N+](C1C=CC([O:39][C:40]([NH:42][C@@H:43]([CH2:61][CH:62]2[CH2:67][CH2:66][CH2:65][CH2:64][CH2:63]2)[C@@H:44]([O:56][Si](C)(C)C)[CH2:45][NH:46][C:47](=[O:55])[O:48][CH2:49][CH2:50][Si:51]([CH3:54])([CH3:53])[CH3:52])=O)=CC=1)([O-])=O>C(Cl)Cl>[Cl:1][C:2]1[C:3]([F:22])=[C:4]([C@:8]([C@@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:40]([NH:42][C@@H:43]([CH2:61][CH:62]3[CH2:63][CH2:64][CH2:65][CH2:66][CH2:67]3)[C@@H:44]([OH:56])[CH2:45][NH:46][C:47](=[O:55])[O:48][CH2:49][CH2:50][Si:51]([CH3:52])([CH3:54])[CH3:53])=[O:39])[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

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 577864902-(trimethylsilyl)ethyl (2S,3S)-3-(4-nitrophenoxycarbonylamino)-4-cyclohexyl-2-(trimethylsilyloxy)butylcarbamateHCID 59382881(S)-1-(3-chloro-2-fluorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol

Product 1

HCID 577864752-(trimethylsilyl)ethyl (2S,3S)-3-((R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-4-cyclohexyl-2-hydroxybutylcarbamateYield 38%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (S)-1-(3-chloro-2-fluorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol (33.0 mg, 0.10 mmol) in CH2Cl2 (2 mL), DIEA (39 mg, 0.30 mmol) was added, followed by the solution of 2-(trimethylsilyl)ethyl (2S,3S)-3-(4-nitrophenoxycarbonylamino)-4-cyclohexyl-2-(trimethylsilyloxy)butylcarbamate in CH2Cl2 (0.8 mL, 0.2 mmol) prepared in the previous step. The resulting yellow solution was stirred at rt for 30 min, and completion of reaction was confirmed by LC-MS. Solvent was removed under vacuum, and the residue was purified by preparative HPLC to give 2-(trimethylsilyl)ethyl (2S,3S)-3-((R)-3-((S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-4-cyclohexyl-2-hydroxybutylcarbamate (25.8 mg, 38%); MS m/z 686 (M+H+).

Workup

  1. customprepared in the previous step
  2. customcompletion of reaction
  3. customSolvent was removed under vacuum
  4. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-70e2bb168aef416589a2bb20822f0282
Source dataset
uspto-grants-2011_01
Patent number
US07872028B2

Reaction notes

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