1,2-Dichloroethane → HCID 57870337, compound

HRID 1698315Notes

Reaction equation

HRID 1698315 reaction equation
Cl.C1C2C(COC([N:19]3[CH2:24][C@@H:23]([C:25](=[O:44])[N:26]([CH:41]4[CH2:43][CH2:42]4)[CH2:27][C:28]4[CH:33]=[CH:32][C:31]([CH3:34])=[C:30]([O:35][CH2:36][CH2:37][CH2:38][O:39][CH3:40])[CH:29]=4)[CH2:22][C@@H:21]([NH2:45])[CH2:20]3)=O)C3C(=CC=CC=3)C=2C=CC=1.[C:46]([N:50]=[C:51]=[O:52])([CH3:49])([CH3:48])[CH3:47].CCN(C(C)C)C(C)C.ClCCCl>C(Cl)Cl>[CH:41]1([N:26]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[C:30]([O:35][CH2:36][CH2:37][CH2:38][O:39][CH3:40])[CH:29]=2)[C:25]([C@H:23]2[CH2:22][C@@H:21]([NH:45][C:51]([NH:50][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:52])[CH2:20][NH:19][CH2:24]2)=[O:44])[CH2:42][CH2:43]1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 62412tert-Butyl isocyanateHCID 81531DiisopropylethylamineHCID 131729670HCID 131729670, compound

Product 1

HCID 57870337HCID 57870337, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of (3R*,5S*)-3-amino-5{-cyclopropyl-[3-(3-methoxy-propoxy)-4-methyl-benzyl]-carbamoyl}-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester, hydrochloride (110 mg, 0.173 mmol), tert-butyl isocyanate (40 μl, 0.35 mmol), DIPEA (34.2 μl, 0.2 mmol) and 1,2-dichloroethane (2 ml) is shaken for 14 h at 50° C. The mixture is diluted with CH2Cl2 and washed with NaHCO3 solution. The organic layer is dried (Na2SO4) and evaporated. The crude product is stirred with a solution of CH2Cl2/piperidine 4:1 (5 mL) for 1 h, the mixture is evaporated and the residue purified by preparative HPLC (C18 column, 10-100% CH3CN+0.1% TFA/H2O+0.1% TFA, 20 min, flow 20 mL 1 min). The combined pure fractions are treated with K2CO3, CH3CN is removed in vacuo, and the residual aqueous phase is extracted three times with CH2Cl2. The combined organic layers are dried (Na2SO4) and evaporated to afford the title compound as a colorless resin. MS: 475.6 [M+H]+; tR (HPLC, Nucleosil C18; 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 8 min, flow 1.5 ml/min): 5.14 min.

Workup

  1. washwashed with NaHCO3 solution
  2. dry with materialThe organic layer is dried (Na2SO4)
  3. customevaporated
  4. stirringThe crude product is stirred with a solution of CH2Cl2/piperidine 4:1 (5 mL) for 1 h
  5. customthe mixture is evaporated
  6. customthe residue purified by preparative HPLC (C18 column, 10-100% CH3CN+0.1% TFA/H2O+0.1% TFA, 20 min, flow 20 mL 1 min)
  7. additionThe combined pure fractions are treated with K2CO3, CH3CN
  8. customis removed in vacuo
  9. extractionthe residual aqueous phase is extracted three times with CH2Cl2
  10. dry with materialThe combined organic layers are dried (Na2SO4)
  11. customevaporated

Sources & evidence

ORD record
ord-077dee5efdf24826a2e5b845964b947d
Source dataset
uspto-grants-2012_04
Patent number
US08163773B2

Reaction notes

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