Triethylamine → HCID 59010013, compound

HRID 1925587Notes

Reaction equation

HRID 1925587 reaction equation
[NH2:1][CH2:2][C:3]([OH:21])([CH2:8][C:9]([C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[O:19][CH3:20])([CH3:11])[CH3:10])[C:4]([F:7])([F:6])[F:5].[CH2:22]([O:29][C:30](ON1C(=O)CCC1=O)=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(CC)CC)C>ClCCl>[C:23]1([CH2:22][O:29][C:30](=[O:31])[NH:1][CH2:2][C:3]([OH:21])([C:4]([F:7])([F:6])[F:5])[CH2:8][C:9]([C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[O:19][CH3:20])([CH3:11])[CH3:10])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 83172Benzyl succinimido carbonateHCID 179365862-(Aminomethyl)-1,1,1-trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-pentanol

Product 1

HCID 59010013HCID 59010013, compoundYield 87.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Racemic 2-(aminomethyl)-1,1,1-trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-pentanol (which may be prepared according to WO03/082827, 894 mg, 2.89 mmol) was dissolved in dichloromethane (15 mL). N-(benzyloxycarbonyloxy)succinimide (1.08 g, 4.34 mmol) was added and the mixture was stirred for 5 min. Triethylamine (804 μL, 5.78 mmol) was added and stirring was continued for 3.5 hours after which time the reaction mixture was washed with saturated sodium bicarbonate solution and evaporated in vacuo. Purification of the residue by Flashmaster II using a 100 g silica cartridge and a solvent gradient of cyclohexane:EtOAc 100:0 to 0:100 over a period of 1 hour gave the racemic product as an oil (1.12 g). This oil was applied to a 2 inch×20 cm Chiralpak AD column eluted with heptane:IPA 97.5:2.5 with a flow rate of 75 mL/min to give Intermediate 7 (2R isomer, 443 mg) after ca. 42 min and Intermediate 8 (2S isomer, 441 mg) after ca. 60 min.

Workup

  1. stirringstirring
  2. waitwas continued for 3.5 hours
  3. washafter which time the reaction mixture was washed with saturated sodium bicarbonate solution
  4. customevaporated in vacuo
  5. customPurification of the residue by Flashmaster II

Sources & evidence

ORD record
ord-a1df27f4ea6e42be9f5db02887a69631
Source dataset
uspto-grants-2012_05
Patent number
US08178573B2

Reaction notes

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