2-Methylbenzenesulfonic acid → (3r,7s,7As)-4-(3-tert-butyl-7-hydroxy-1-oxo-tetrahydro-pyrrolo[1,2-c]imidazol-2-yl)-naphthalene-1-carbonitrile

HRID 434077Notes

Reaction equation

HRID 434077 reaction equation
[C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([NH:13][C:14]([C@@H:16]2[C@@H:20]([OH:21])[CH2:19][CH2:18][NH:17]2)=[O:15])=[CH:5][CH:4]=1)#[N:2].[CH:22](=O)[C:23]([CH3:26])([CH3:25])[CH3:24].C1(C)C(S(O)(=O)=O)=CC=CC=1>C1C=CC=CC=1.CCCCC>[C:23]([C@@H:26]1[N:17]2[CH2:18][CH2:19][C@H:20]([OH:21])[C@H:16]2[C:14](=[O:15])[N:13]1[C:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]([C:1]#[N:2])=[CH:4][CH:5]=1)([CH3:25])([CH3:24])[CH3:22]

Participants

6

Reactant 3

HCID 69252-Methylbenzenesulfonic acidHCID 12417Pivalaldehyde2×HCID 59119502(2S,3S) 3-Hydroxy-pyrrolidine-2-carboxylic acid (4-cyano-naphthalen-1-yl)-amide

Product 1

HCID 58583619(3r,7s,7As)-4-(3-tert-butyl-7-hydroxy-1-oxo-tetrahydro-pyrrolo[1,2-c]imidazol-2-yl)-naphthalene-1-carbonitrileYield 81.8%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolvent2×HCID 8003PentaneSolvent

Procedure

A suspension of 30D (40 mg, 0.14 mmol) and pivalaldehyde (30 μl, 0.27 mmol) in a mixture of dry benzene (0.5 ml) and dry pentane (5.0 ml) was refluxed for 20 hr with a Dean-Starke receiver, after which additional pivalaldehyde (30 μl, 0.27 mmol), dry benzene (0.5 ml) and catalytic toluenesulfonic acid was added (Ref: Org. Lett. 2 (18) 2781-2783, (2000)). The reaction mixture was refluxed for another 25 hr, evaporated to dryness and dried in vacuo. Purification using automated flash chromatography (10 g silica gel column, EtOAc/hexane gradient) gave the title compound (single diastereoisomer) as a white foam (40 mg, 81.8%). MS (ES): m/z 350 [M+1]+.

Workup

  1. temperaturewas refluxed for 20 hr with a Dean-Starke receiver
  2. temperatureThe reaction mixture was refluxed for another 25 hr
  3. customevaporated to dryness
  4. customdried in vacuo
  5. customPurification

Sources & evidence

ORD record
ord-73584670b9754750b08b26e240fd8992
Source dataset
uspto-grants-2003_12
Patent number
US06670386B2

Reaction notes

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