1-Hydroxybenzotriazole → tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

HRID 278266Notes

Reaction equation

Cl.[CH3:2][NH:3][O:4][CH3:5].C1C=CC2N(O)N=NC=2C=1.[C:16]([N:23]1[CH2:31][CH2:30][CH:26]([C:27]([OH:29])=O)[CH2:25][CH2:24]1)([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].C(N(C(C)C)CC)(C)C.CCN=C=NCCCN(C)C.Cl>O.CN(C=O)C>[C:19]([O:18][C:16]([N:23]1[CH2:24][CH2:25][CH:26]([C:27]([N:3]([CH3:2])[O:4][CH3:5])=[O:29])[CH2:30][CH2:31]1)=[O:17])([CH3:20])([CH3:21])[CH3:22]

Participants

Conditions

Temperature: 18 °C

Procedure

A 100 L round-bottomed-flask equipped with a mechanical stirrer, thermocouple and nitrogen inlet was charged with DMF (51 L), N,O-dimethylhydroxyamine hydrochloride (2.62 Kg, 26.55 mol), HOBT (1.2 Kg, 8.85 mol), and N-Boc isonipecotic acid (4.10 Kg, 17.70 mol). The mixture warmed to 18 ° C. as the diisopropylethylamine (4.60 Kg, 6.2 L, 35.41 mol) was added over 15 min. The EDC.HCl (5.09 Kg, 26.55 mol) was added in three portions over 3 h maintaining an internal temperature of 18° C. with gentle cooling. The reaction mixture was held at 18° C. for 12 h. HPLC analysis shows no remaining 1. The reaction mixture was pumped into an extractor containing 74 L of water at 5° C. The resulting solution (39.3 g/L of 2) was extracted with ethyl acetate (4×37 L).

Workup

customA 100 L round-bottomed-flask equipped with a mechanical stirrer
additionwas added over 15 min
extractionThe resulting solution (39.3 g/L of 2) was extracted with ethyl acetate (4×37 L)

Sources & evidence

ORD record: ord-b3c3ca2c9d9b4daf8a75ed94a54b6db4
Source dataset: uspto-grants-2002_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06358979B1

Reaction notes

Loading…