tert-butyl N-(prop-2-yn-1-yl)carbamate → HCID 86641445, compound

HRID 1189940Notes

Reaction equation

HRID 1189940 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]([CH2:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[C:9](=[O:14])[C:10]([F:13])([F:12])[F:11])[CH:5]=[CH:6][CH:7]=1.[CH2:22]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[C:23]#[CH:24]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I.C(N(CC)CC)C>[CH:16]1([CH2:15][N:8]([C:4]2[CH:3]=[C:2]([C:24]#[C:23][CH2:22][NH:25][C:26](=[O:32])[O:27][C:28]([CH3:30])([CH3:29])[CH3:31])[CH:7]=[CH:6][CH:5]=2)[C:9](=[O:14])[C:10]([F:13])([F:12])[F:11])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

6

Reactant 2

HCID 11073648tert-butyl N-(prop-2-yn-1-yl)carbamateHCID 86641443HCID 86641443, compound

Product 1

HCID 86641445HCID 86641445, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
90 °C

Procedure

Triethylamine (45 mL) was added to a mixture of N-(3-bromophenyl)-N-(cyclohexylmethyl)-2,2,2-trifluoroacetamide (3.8 g, 10.4 mmol), tert-butyl prop-2-ynylcarbamate (2.42 g, 15.6 mmol), Pd(Ph3P)4 (0.6 g, 0.52 mmol) and CuI (0.1 g, 0.52 mmol) and flushed for 15 min with argon. The reaction mixture was stirred for 16 h at 90° C. The reaction mixture was cooled, diluted with ethyl acetate and filtered through Celite bed and the filtrate was concentrated under reduced pressure. Purification by column chromatography (100-200 silica mesh 5% to 10% EtOAc—hexane) gave tert-butyl 3-(3-(N-(cyclohexylmethyl)-2,2,2-trifluoroacetamido)phenyl)prop-2-ynylcarbamate as a yellow semi-solid. Yield (2.1 g, 50%); 1H NMR (400 MHz, DMSO-d6) δ 7.49-7.48 (m, 2H), 7.43-7.41 (m, 2H), 3.99 (bs, 2H), 3.58 (bs, 2H), 1.64-1.57 (m, 6H), 1.39 (s, 9H), 1.19-1.12 (m, 3H), 0.95-0.89 (m, 2H).

Workup

  1. customflushed for 15 min with argon
  2. temperatureThe reaction mixture was cooled
  3. additiondiluted with ethyl acetate
  4. filtrationfiltered through Celite bed
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customPurification by column chromatography (100-200 silica mesh 5% to 10% EtOAc—hexane)

Sources & evidence

ORD record
ord-e8c4887e2b8c487c989b58fb66b7a198
Source dataset
uspto-grants-2014_03
Patent number
US08674137B2

Reaction notes

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