4-Methylmorpholine → (2S,3S)-3-(tert-Butyl-dimethyl-silanyloxy)-2-(4-cyano-naphthalen-1-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 434075Notes

Reaction equation

C(OC(Cl)=O)C(C)C.[C:9]([O:13][C:14]([N:16]1[CH2:20][CH2:19][C@H:18]([O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[C@H:17]1[C:29]([OH:31])=O)=[O:15])([CH3:12])([CH3:11])[CH3:10].CN1CCOCC1.[NH2:39][C:40]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[C:43]([C:50]#[N:51])=[CH:42][CH:41]=1>CCOC(C)=O>[C:9]([O:13][C:14]([N:16]1[CH2:20][CH2:19][C@H:18]([O:21][Si:22]([C:25]([CH3:27])([CH3:26])[CH3:28])([CH3:23])[CH3:24])[C@H:17]1[C:29](=[O:31])[NH:39][C:40]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[C:43]([C:50]#[N:51])=[CH:42][CH:41]=1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

Conditions

Temperature: -20 °C

Procedure

A solution of isobutylchloroformate (0.75 ml, 5.8 mmol) in dry EtOAc (8.0 ml) was cooled to −20° C., treated dropwise with a mixture of 30B (2.0 g, 5.8 mmol) and N-methylmorpholine (0.64 ml, 5.8 mmol) in dry EtOAc (6.0 ml) over a period of 45 minutes. The mixture was stirred at −20° C. for 30 minutes, then treated dropwise over a period of 1.5 h with a solution of 4-aminonaphthalene carbonitrile (976 mg, 5.8 mmol) in dry EtOAc (35 ml). The reaction mixture was stirred at −20° C. for an additional 3.0 h, then at RT for 4 days after which it was partitioned between water (50 ml) and EtOAc (3×250 ml). Purification by flash chromatography provided the title compound as a dark pink foam (2.19 g, 76.3%). MS (ES): m/z 496 [M+1]+.

Workup

stirringThe reaction mixture was stirred at −20° C. for an additional 3.0 h
customat RT for 4 days after which it was partitioned between water (50 ml) and EtOAc (3×250 ml)
customPurification by flash chromatography

Sources & evidence

ORD record: ord-53b48c7a6c494de189eb02d004e3a171
Source dataset: uspto-grants-2003_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06670386B2

Reaction notes

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