Acetic Anhydride → N-ethyl-3-fluoroaniline

HRID 741643Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[C:9](O[C:13](=O)[CH3:14])(=O)[CH3:10].[CH2:16]([N:19]1[C@H:24]([CH3:25])[CH2:23][N:22]([C@H:26]([C:41]2[CH:42]=[C:43]([CH:47]=[CH:48][CH:49]=2)[C:44](Cl)=[O:45])[C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([O:33][Si](C(C)(C)C)(C)C)[CH:28]=2)[C@@H:21]([CH3:50])[CH2:20]1)[CH:17]=[CH2:18]>>[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH:5][CH2:9][CH3:10].[CH2:16]([N:19]1[C@H:24]([CH3:25])[CH2:23][N:22]([C@H:26]([C:41]2[CH:42]=[C:43]([CH:47]=[CH:48][CH:49]=2)[C:44]([N:5]([CH2:13][CH3:14])[C:4]2[CH:6]=[CH:7][CH:8]=[C:2]([F:1])[CH:3]=2)=[O:45])[C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([OH:33])[CH:28]=2)[C@@H:21]([CH3:50])[CH2:20]1)[CH:17]=[CH2:18]

Participants

Reactant 3

HCID 7918Acetic Anhydride

HCID 97423-Fluoroaniline

HCID 111350383-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-(tert-butyldimethylsilyloxy)benzyl)benzoyl chloride

Product 2

HCID 11062466N-ethyl-3-fluoroaniline

HCID 57187734(+)-3-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-ethyl-N-(3-fluorophenyl)benzamide

Procedure

3-Fluoro-N-ethylaniline [NMR (DMSO-d6, 200 MHz): δ1.18 (t, J=7.2 Hz, 3H); 3.02 (dq, J1 =7.2 Hz, J2 =7.2 Hz, 2H); 5.86 (br m, 1H); 6.24-6.42 (m, 3H); 7.07 (q, J=7.8 Hz, 1H)] was prepared from 3-fluoroaniline and acetic anhydride, coupled with 3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-(tert-butyldimethylsilyloxy)benzyl)benzoyl chloride, deprotected and purified by the methods described in Example 10 to give (+)-3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-ethyl-N-(3-fluorophenyl)benzamide as a white solid. NMR (DMSO-d6, 200 MHz): δ0.92 (d, J=6 Hz, 3H); 0.96 (d, J=6 Hz, 3H); 1.05 (t, J=7 Hz, 3H); 1.7 (m, 1H); 2.05 (m, 1H); 2.3 (m, 1H); 2.5 (m, 2H); 2.7 (m, 1H); 2.9 (m, 1H); 3.2 (m, 1H); 3.9 (q, J=7 Hz, 2H); 4.8 (s, 1H); 5.1 (d, J=10 Hz, 1H); 5.2 (d, J=16 Hz, 1H); 5.8 (m, 1H); 6.45 (d, J=8 Hz, 1H); 6.6 (s, 1H); 6.65 (d, J=8 Hz, 1H); 6.9 (d, J=8 Hz, 1H); 7.0-7.2 (m, 3H); 7.2-7.4 (m, 5H); 9.35 (s, 1H). [α]D20 =+4.3° (abs EtOH, c=3.9). Calc. for C31H36FN3O2HCl 0.5 H2O: C, 68.06; H, 7.00: N, 7.68; Cl, 6.48. Found C, 68.10;H, 7.04; N, 7.63; Cl, 6.42. Mass spectrum (CI--CH4) m/e: 502 (M+1, 39%), 501 (M, 9%), 348 (29%), 153 (100%).

Workup

custompurified by the methods

Sources & evidence

ORD record: ord-5a304c7e129a46a1b76ca9926de9f2f7
Source dataset: uspto-grants-1996_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05552404

Reaction notes

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