Methyl (2Z)-2-[(tert-butoxycarbonyl)amino]-3-[4-(2-tert-butyl-1,1-dioxido-3-oxoisothiazolidin-5-yl)-3-fluorophenyl]acrylate → Methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-[4-(2-tert-butyl-1,1-dioxido-3-oxoisothiazolidin-5-yl)-3-fluorophenyl]propanoate

HRID 724735Notes

Reaction equation

HRID 724735 reaction equation
[C:1]([O:5][C:6]([NH:8]/[C:9](=[CH:14]\[C:15]1[CH:20]=[CH:19][C:18]([CH:21]2[S:25](=[O:27])(=[O:26])[N:24]([C:28]([CH3:31])([CH3:30])[CH3:29])[C:23](=[O:32])[CH2:22]2)=[C:17]([F:33])[CH:16]=1)/[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)C.[B-](F)(F)(F)F.COC1C([P@](CC[P@](C2C=CC=CC=2)C2C(OC)=CC=CC=2)C2C=CC=CC=2)=CC=CC=1.C1CC=CCCC=C1.[Rh]>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]2[S:25](=[O:26])(=[O:27])[N:24]([C:28]([CH3:31])([CH3:30])[CH3:29])[C:23](=[O:32])[CH2:22]2)=[C:17]([F:33])[CH:16]=1)[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

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

Product 1

HCID 58746807Methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-[4-(2-tert-butyl-1,1-dioxido-3-oxoisothiazolidin-5-yl)-3-fluorophenyl]propanoateYield 92%

Reagents, catalysts & solvents 2

HCID 10930696(1Z,5Z)-cycloocta-1,5-diene;(R)-(2-methoxyphenyl)-[2-[(2-methoxyphenyl)-phenylphosphanyl]ethyl]-phenylphosphane;rhodium;tetrafluoroborateCatalystHCID 702EthanolSolvent

Procedure

Methyl (2Z)-2-[(tert-butoxycarbonyl)amino]-3-[4-(2-tert-butyl-1,1-dioxido-3-oxoisothiazolidin-5-yl)-3-fluorophenyl]acrylate (1.24 g, 2.56 mmol) in ethanol (100 mL) was degassed and (R,R)-(−)-1,2-bis[(o-methoxyphenyl)(phenyl)phosphino]ethane(1,5-cyclooctadiene) rhodium (I) tetrafluroborate (58 mg, 0.077 mmol) was added under nitrogen. The solution was placed under a hydrogen atmosphere (50 psi) and shaken for 16 h. The solution was concentrated in vacuo and purified by silica gel chromatography (10–40% ethyl aceate:hexanes) to afford product as a white foam (1.14 g, 92%). 1H NMR (400 MHz, CDCl3): δ 7.29–7.27 (m, 1H), 7.03–6.95 (m, 2H), 5.06–5.02 (m, 2H), 4.61–4.57 (brs, 1H), 3.73 (s, 3H), 3.31–3.27 (m, 1H), 3.15–3.06 (m, 3H), 1.66 (s, 9H), 1.42 (s, 9H). LCMS found for C22H32FN2NaO7S (M+Na)+: m/z=509.

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. custompurified by silica gel chromatography (10–40% ethyl aceate:hexanes)

Sources & evidence

ORD record
ord-672dd2f6f06d4da5a4f313d498aa81b8
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

Loading…