Diisopropylethylamine → {(3S,5S)-1-((S)-2-tert-butoxycarbonylamino-2-cyclohexyl-acetyl)-5-[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-pyrrolidin-3-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester

https://huagongshe.com/reaction/1481912

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	N-(tert-Butoxycarbonyl)-L-cyclohexylglycine	HCID 7004938	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	{(3S,5S)-5-[(R)-(1,2,3,4-Tetrahydro-naphthalen-1-yl)carbamoyl]-pyrrolidin-3-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester trifluoroacetate	HCID 90220816	—
Solvent	Dimethylformamide	HCID 6228	—
Product	{(3S,5S)-1-((S)-2-tert-butoxycarbonylamino-2-cyclohexyl-acetyl)-5-[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-pyrrolidin-3-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester	HCID 90220880	—

Reaction Conditions

Temperature	0 °C

Reaction Steps

To a solution of (S)-tert-butoxycarbonylamino-cyclohexyl-acetic acid (Aldrich) (4.529 g, 17.622 mmol) in DMF (100 mL) were added HATU (6.7 g, 17.622 mmol) followed by DIPEA (13.87 mL, 80.101 mmol). The mixture was cooled to 0° C. and ({(3S,5S)-5-[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-pyrrolidin-3-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester trifluoroacetate (Intermediate 22) (9.5 g, 16.02 mmol) in DMF (50 mL) was added dropwise and then the cooling bath removed. After 4 h the mixture was diluted with ethyl acetate, washed with water, dried over sodium sulfate and concentrated to give the title compound as an off white solid (10 g) which was used without purification. LC-MS: 721 (M+H).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09409888B2
Source dataset	uspto-grants-2016_08
ORD ID	ord-21a17a61a9ef420086a2d45e0d3748bf
Source note	uspto-grants-2016_08