4-Methylmorpholine → HCID 59936697, compound

HRID 568093Notes

Reaction equation

HRID 568093 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH:16]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:17]([OH:19])=O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.[NH2:35][CH2:36][CH2:37][N:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1.C(OCC)(=O)C>CN(C=O)C>[C:24]([O:23][C:21](=[O:22])[NH:20][C@H:16]([C:17](=[O:19])[NH:35][CH2:36][CH2:37][N:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1)[CH2:15][C:12]1[CH:11]=[CH:10][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:14][CH:13]=1)([CH3:27])([CH3:26])[CH3:25]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 8857Ethyl AcetateHCID 33944N-(2-Aminoethyl)piperidineHCID 294897Boc-O-benzyl-D-tyrosine

Product 1

HCID 59936697HCID 59936697, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 27.9 g (75 mmol) 3-(4-benzyloxy-phenyl)-2-tert-butoxycarbonylamino-propionic acid, (Bachem Inc., Torrance, Calif. 90505) 16.5 mL (150 mmol) 4-methylmorpholine, and 28.5 g (75 mmol) O-Benzotriazol-1-yl-N,N,N′,N′-bis(tetramethylene)uronium hexafluorophosphate in 110 mL dry DMF was stirred in an ice-bath for 30 minutes. Next, 10.7 mL (75 mmol) of 1-(2-aminoethyl)piperidine (Aldrich, Milwaukee, Wis.) was added, and the resulting solution was warmed to 25° C. and stirred 60 minutes. The mixture was poured into 200 mL ethyl acetate, and washed sequentially with 200 mL each of 2.5% aqueous HCl solution, brine, saturated aqueous sodium bicarbonate solution, and finally twice with brine. The mixture was then dried over anhydrous sodium sulfate and concentrated at reduced pressure to give 33.7 g (94%) of (S)-[2-(4-benzyloxy-phenyl)-1-(2-piperidin-1-yl-ethylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester as a pale amber solid; mp 54-61° C.

Workup

  1. washwashed sequentially with 200 mL each of 2.5% aqueous HCl solution, brine, saturated aqueous sodium bicarbonate solution
  2. dry with materialThe mixture was then dried over anhydrous sodium sulfate
  3. concentrationconcentrated at reduced pressure

Sources & evidence

ORD record
ord-d0b7bb23a5cf4189b990a23480f11961
Source dataset
uspto-grants-2001_01
Patent number
US06180677B2

Reaction notes

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