1,8-Diazabicyclo(5.4.0)undec-7-ene → Methyl (2Z)-2-[(tert-butoxycarbonyl)amino]-3-[4-(2-tert-butyl-1,1-dioxido-3-oxoisothiazolidin-5-yl)-3-fluorophenyl]acrylate

HRID 724734Notes

Reaction equation

HRID 724734 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9](P(OC)(OC)=O)[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].N12CCCN=C1CCCCC2.[C:31]([N:35]1[C:39](=[O:40])[CH2:38][CH:37]([C:41]2[CH:48]=[CH:47][C:44]([CH:45]=O)=[CH:43][C:42]=2[F:49])[S:36]1(=[O:51])=[O:50])([CH3:34])([CH3:33])[CH3:32]>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8]/[C:9](=[CH:45]\[C:44]1[CH:47]=[CH:48][C:41]([CH:37]2[S:36](=[O:51])(=[O:50])[N:35]([C:31]([CH3:32])([CH3:34])[CH3:33])[C:39](=[O:40])[CH2:38]2)=[C:42]([F:49])[CH:43]=1)/[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 397380Methyl ((tert-butoxy(hydroxy)methylidene)amino)(dimethoxyphosphoryl)acetateHCID 116166194-(2-tert-Butyl-1,1-dioxido-3-oxoisothiazolidin-5-yl)-3-fluorobenzaldehyde

Product 1

HCID 11576683Methyl (2Z)-2-[(tert-butoxycarbonyl)amino]-3-[4-(2-tert-butyl-1,1-dioxido-3-oxoisothiazolidin-5-yl)-3-fluorophenyl]acrylateYield 77.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Methyl [(tert-butoxycarbonyl)amino](dimethoxyphosphoryl)acetate (3.53 g, 11.9 mmol) in methylene chloride (180 mL) was treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (1.92 mL, 12.9 mmol). After five minutes 4-(2-tert-butyl-1,1-dioxido-3-oxoisothiazolidin-5-yl)-3-fluorobenzaldehyde (3.1 g, 9.9 mmol) was added and the solution stirred at rt for 1 h. The solution was diluted with methylene chloride (50 mL), washed with 1 N aqueous hydrochloric acid solution (250 mL), and the organic phase dried over sodium sulfate. Purification by silica gel chromatography (5–25% ethyl acetate:hexanes) afforded product as a white foam (3.7 g, 77%). 1H NMR (400 MHz, CDCl3): δ 7.35–7.29 (m, 3H), 7.17 (s, 1H), 5.04 (dd, J=9.0, 7.1 Hz, 1H), 3.87 (s, 3H), 3.29 (dd, J=17.2, 9.0 Hz, 1H), 3.17 (dd, J=17.2, 7.0 Hz, 1H), 1.65 (s, 9H), 1.39 (s, 9H). LCMS found for C22H30FN2NaO7S (M+Na)+: m/z=507.

Workup

  1. washwashed with 1 N aqueous hydrochloric acid solution (250 mL)
  2. dry with materialthe organic phase dried over sodium sulfate
  3. customPurification by silica gel chromatography (5–25% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-b5e4decf8a144783addf527d62d04b4e
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

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