Dicyclohexylcarbodiimide → 4,4,4-Trifluoro-3-methyl-but-2-enoic acid {2-[5-(tert-butyl-dimethyl-silanyloxy)-8a-methyl-decahydro-naphthalen-1-yl]-propyl}-amide

HRID 1638228Notes

Reaction equation

HRID 1638228 reaction equation
[C:1]([Si:5]([CH3:23])([CH3:22])[O:6][C@H:7]1[CH2:16][CH2:15][CH2:14][C@@:13]2([CH3:17])[C@H:8]1[CH2:9][CH2:10][CH2:11][C@@H:12]2[C@H:18]([CH3:21])[CH2:19][NH2:20])([CH3:4])([CH3:3])[CH3:2].[F:24][C:25]([F:34])([F:33])[C:26](O)([CH3:31])[CH2:27][C:28](O)=[O:29].C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl>[C:1]([Si:5]([CH3:23])([CH3:22])[O:6][CH:7]1[CH2:16][CH2:15][CH2:14][C:13]2([CH3:17])[CH:8]1[CH2:9][CH2:10][CH2:11][CH:12]2[CH:18]([CH3:21])[CH2:19][NH:20][C:28](=[O:29])[CH:27]=[C:26]([CH3:31])[C:25]([F:34])([F:33])[F:24])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 1361684,4,4-Trifluoro-3-hydroxy-3-methylbutanoic acidHCID 57261774(S)-2-[(1R,4aR,5S,8aR)-5-(tert-Butyl-dimethyl-silanyloxy)-8a-methyl-decahydro-naphthalen-1-yl]-propylamine

Product 1

HCID 572977674,4,4-Trifluoro-3-methyl-but-2-enoic acid {2-[5-(tert-butyl-dimethyl-silanyloxy)-8a-methyl-decahydro-naphthalen-1-yl]-propyl}-amideYield 15.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

701 mg (2.06 mmol) of (S)-2-[(1R,4aR,5S,8aR)-5-(tert-Butyl-dimethyl-silanyloxy)-8a-methyl-decahydro-naphthalen-1-yl]-propylamine, 532 mg (1.5 eq.) of rac-3-trifluoromethyl-3-hydroxy-butyric acid, and 50 mg (0.2 eq.) of DMAP (N,N-dimethylaminopyridine) were dissolved in 20 ml of CH2Cl2. At 0° 680 mg (1.6 eq.) of DCC (dicyclohexylcarbodiimide) was added and the mixture allowed to react for 4 h at ambient temperature. The precipitated urea was filtered off and the filtrate evaporated to dryness. Flash chromatography (SiO2, hexane/AcOEt=85/15) yielded in the less polar fractions 149 mg of unwanted 4,4,4-trifluoro-3-methyl-but-2-enoic acid {2-[5-(tert-butyl-dimethyl-silanyloxy)-8a-methyl-decahydro-naphthalen-1-yl]-propyl}-amide and in the more polar ones 811 mg of the title compound as colorless oil. Medium pressure chromatography of the latter (SiO2, hexane/AcOEt=90/10) gave in the less polar fractions 367 mg of the (R)-butyramide and in the more polar ones 314 mg of the (S)-isomer, both as white foam. For determination of abs. configuration see d] below.

Workup

  1. customto react for 4 h at ambient temperature
  2. filtrationThe precipitated urea was filtered off
  3. customthe filtrate evaporated to dryness

Sources & evidence

ORD record
ord-f1c1bda672b6400799a9ee377935f238
Source dataset
uspto-grants-2000_03
Patent number
US06043385

Reaction notes

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