Methyl iodide → HCID 16110593, compound

HRID 495675Notes

Reaction equation

HRID 495675 reaction equation
[C:1]([Si:5]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[O:6][CH2:7][CH2:8][C:9]1[C:10](=[O:34])[NH:11][C:12]2[C:17]([C:18]=1[C:19]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=1[O:26][C:27](=[O:29])[CH3:28])=[CH:16][C:15]([C:30]([F:33])([F:32])[F:31])=[CH:14][CH:13]=2)([CH3:4])([CH3:3])[CH3:2].CI.[C:49]([O-])([O-])=O.[K+].[K+]>CC(C)=O.C(OCC)(=O)C>[C:1]([Si:5]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)([C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)[O:6][CH2:7][CH2:8][C:9]1[C:10](=[O:34])[N:11]([CH3:49])[C:12]2[C:17]([C:18]=1[C:19]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=1[O:26][C:27](=[O:29])[CH3:28])=[CH:16][C:15]([C:30]([F:31])([F:33])[F:32])=[CH:14][CH:13]=2)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 16110586HCID 16110586, compound

Product 1

HCID 16110593HCID 16110593, compound

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of the product from step A (6.82 g, 10.3 mmol), methyl iodide (4.37 g, 30.8 mmol) and K2CO3 (3.05 g, 30.8 mmol) in acetone (200 mL) at ambient temperature was stirred for 18 hours. At the end diluted with ethyl acetate (200 mL), washed with water (100 mL), brine (100 mL) and dried. Chromatography with gradient elution (SiO2) using hexanes, ethyl acetate (90:10 to 70:30) afforded the compound of Step B as the major product (5.52 g, 8.1 mmol, 79%, Rt=2.3 minutes C18 LC) as white solid. MS [M+H]=678. 1H NMR (CD3OD) δ 7.82 (d, J=8.1 Hz, 1H), 7.73 (d, J=8.9 Hz, 1H), 7.52 (d, J=9.2 Hz, 1H), 7.48 (m, 4H), 7.34 (m, 3H), 7.21 (m, 6H), 3.91 (m, 1H), 3.76 (m, 4H), 2.88 (m, 1H), 2.70 (m, 1H), 1.71 (s, 3H), 0.94 (s, 9H). A minor product characterized as the O-methyl derivative had the following characteristics. MS [M+H]=678. 1H NMR (CD3OD) δ 7.82 (d, J=8.1 Hz, 1H), 7.95 (d, J=5.1 Hz, 1H), 7.52 (d, J=9.2 Hz, 1H), 7.48 (m, 4H), 7.34 (m, 3H), 7.21 (m, 6H), 3.91 (m, 1H), 3.76 (m, 4H), 2.88 (m, 1H), 2.70 (m, 1H), 1.71 (s, 3H), 0.94 (s, 9H). The ratio of the N-methyl derivative to the O-methyl derivative was approximately 9:1.

Workup

  1. washwashed with water (100 mL), brine (100 mL)
  2. customdried
  3. washChromatography with gradient elution (SiO2)

Sources & evidence

ORD record
ord-230edf4683b7487fbdb6f89ef40d6c70
Source dataset
uspto-grants-2005_09
Patent number
US06939968B2

Reaction notes

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