Dichloromethane → HCID 59201400, compound

HRID 451886Notes

Reaction equation

HRID 451886 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@:9]([C@@H:18]1[CH2:23][CH2:22][CH2:21][N:20]([C:24](=[O:45])[NH:25][C@H:26]([CH2:35][N:36]([CH3:44])C(OC(C)(C)C)=O)[C@H:27]([CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)[OH:28])[CH2:19]1)([OH:17])[CH2:10][CH2:11][CH2:12][NH:13]C(=O)[O-].[C:46]([OH:52])(C(F)(F)F)=[O:47].[CH2:53](Cl)Cl>>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@:9]([C@@H:18]1[CH2:23][CH2:22][CH2:21][N:20]([C:24](=[O:45])[NH:25][C@H:26]([CH2:35][NH:36][CH3:44])[C@H:27]([CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)[OH:28])[CH2:19]1)([OH:17])[CH2:10][CH2:11][CH2:12][NH:13][C:46](=[O:47])[O:52][CH3:53]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 86639455HCID 86639455, compound

Product 1

HCID 59201400HCID 59201400, compoundYield 84%

Conditions

Temperature
0 °C

Procedure

(S)-4-(2-chloro-3-fluorophenyl)-4-((R)-1-((1S,2R)-1-cyclohexyl-1-hydroxy-3-(N-methyl-N-(t-butoxycarbonyl)amino)propan-2-ylcarbamoyl)piperidin-3-yl)-4-hydroxybutylcarbamate (70 mg, 0.104 mmol) was cooled to 0° C. and a 20% solution of TFA in CH2Cl2 (5 mL) was added. The mixture was stirred at 0° C. for about 20 min and quenched with satd aq NaHCO3. The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (3×). The combined organic layers were washed with brine, then concentrated in vacuo to give crude product, which was purified by preparative HPLC to afford methyl (S)-4-(2-chloro-3-fluorophenyl)-4-((R)-1-((1S,2R)-1-cyclohexyl-1-hydroxy-3-(methylamino)propan-2-ylcarbamoyl)piperidin-3-yl)-4-hydroxybutylcarbamate (50 mg, yield 84%). 1H NMR (400 MHz, MeOD): 0.90-1.87 (m, 18H), 1.87-2.08 (m, 2H), 2.10-2.22 (s, 1H), 2.60-2.72 (t, 1H), 2.72 (s, 3H), 2.75-2.85 (t, 1H), 2.90-3.10 (m, 3H), 3.40-3.47 (m, 1H), 3.60 (s, 3H), 3.90-4.05 (d, 1H), 4.05-4.15 (m, 1H), 4.25-4.40 (d, 1H), 7.10-7.20 (s, 1H), 7.32-7.41 (t, 1H), 7.50-7.60 (t, 1H). MS (E/Z): 571.35 (M+H+).

Workup

  1. customquenched with satd aq NaHCO3
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with CH2Cl2 (3×)
  4. washThe combined organic layers were washed with brine
  5. concentrationconcentrated in vacuo
  6. customto give crude product, which
  7. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-3e638cdebe9349f3ad8428a9f780c9b4
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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