Diisopropylethylamine → (1R,3S)-4-chloro-5-(3,4-difluorophenyl)-N-(3-hydroxycyclohexyl)isoxazole-3-carboxamide

HRID 1510425Notes

Reaction equation

HRID 1510425 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][C@H:4]([OH:8])[CH2:3]1.C(N(CC)C(C)C)(C)C.[Cl:18][C:19]1[C:20]([C:32](Cl)=[O:33])=[N:21][O:22][C:23]=1[C:24]1[CH:29]=[CH:28][C:27]([F:30])=[C:26]([F:31])[CH:25]=1>ClCCl>[Cl:18][C:19]1[C:20]([C:32]([NH:1][C@@H:2]2[CH2:7][CH2:6][CH2:5][C@H:4]([OH:8])[CH2:3]2)=[O:33])=[N:21][O:22][C:23]=1[C:24]1[CH:29]=[CH:28][C:27]([F:30])=[C:26]([F:31])[CH:25]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 25630532(1S,3R)-3-aminocyclohexanolHCID 866520824-Chloro-5-(3,4-difluorophenyl)-isoxazole-3-carbonyl chloride

Product 1

HCID 25181768(1R,3S)-4-chloro-5-(3,4-difluorophenyl)-N-(3-hydroxycyclohexyl)isoxazole-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A suspension of (1S,3R)-3-aminocyclohexanol (46 mg, 0.40 mmol), N,N-diisopropylethylamine (0.21 mL, 1.20 mmol) and dichloromethane (15 mL) under argon was treated with a dichloromethane (15 mL) solution of 4-chloro-5-(3,4-difluorophenyl)-isoxazole-3-carbonyl chloride (112 mg, 0.40 mmol) at room temperature. After stirring for 2 hours the volatiles were removed in vacuo, and the residue was purified initially by silica gel chromatography, eluting with dichloromethane to 4% methanol in dichloromethane followed by RP HPLC (H2O/MeCN/MeOH 48/48/4 [vol./vol.]) to afford the title compound: (86 mg, 0.24 mmol).

Workup

  1. customwere removed in vacuo
  2. customthe residue was purified initially by silica gel chromatography
  3. washeluting with dichloromethane to 4% methanol in dichloromethane

Sources & evidence

ORD record
ord-a1cd66b62036402da3ee5c7a2f21816b
Source dataset
uspto-grants-2012_07
Patent number
US08211927B2

Reaction notes

Loading…