Fluoroacetyl chloride → 2-fluoro-N-(3-{[2-((1S,2S)-6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-ethyl]-methyl-amino}-propyl)-N-(3-methoxy-2-methoxymethyl-2-methyl-propyl)-acetamide

HRID 2090571Notes

Reaction equation

HRID 2090571 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C@H:8]([CH:12]([CH3:14])[CH3:13])[C@:7]([CH2:16][CH2:17][N:18]([CH2:20][CH2:21][CH2:22][NH:23][CH2:24][C:25]([CH2:30][O:31][CH3:32])([CH3:29])[CH2:26][O:27][CH3:28])[CH3:19])([OH:15])[CH2:6][CH2:5]2.CCN(C(C)C)C(C)C.[F:42][CH2:43][C:44](Cl)=[O:45]>C(Cl)Cl>[F:42][CH2:43][C:44]([N:23]([CH2:22][CH2:21][CH2:20][N:18]([CH2:17][CH2:16][C@@:7]1([OH:15])[CH2:6][CH2:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([F:1])[CH:3]=2)[C@@H:8]1[CH:12]([CH3:14])[CH3:13])[CH3:19])[CH2:24][C:25]([CH2:26][O:27][CH3:28])([CH3:29])[CH2:30][O:31][CH3:32])=[O:45]

Participants

5

Reactant 3

HCID 9663Fluoroacetyl chlorideHCID 81531DiisopropylethylamineHCID 67337353(1S,2S)-6-fluoro-1-isopropyl-2-(2-{[3-(3-methoxy-2-methoxymethyl-2-methyl-propylamino)-propyl]-methyl-amino}-ethyl)-1,2,3,4-tetrahydro-naphthalen-2-ol

Product 1

HCID 673391152-fluoro-N-(3-{[2-((1S,2S)-6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-ethyl]-methyl-amino}-propyl)-N-(3-methoxy-2-methoxymethyl-2-methyl-propyl)-acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2.73 g of (1S,2S)-6-fluoro-1-isopropyl-2-(2-{[3-(3-methoxy-2-methoxymethyl-2-methyl-propylamino)-propyl]-methyl-amino}-ethyl)-1,2,3,4-tetrahydro-naphthalen-2-ol in DCM (29 mL) was added at 0° C., 1.5 mL of DIPEA and 1.1 mL of fluoroacetyl chloride. The mixture was stirred for 20 min at 0° C. then allowed to warm up to rt for 1 h and quenched with sat.-NaHCO3. The organic phase was dried over anh. Na2SO4 and concentrated in vacuo. The resulting crude ester was dissolved in EtOH (29 mL) and treated with 15 mL of a 1M NaOH solution. The mixture was stirred for 15 min at rt and concentrated in vacuo. The resulting residue was taken up in DCM and washed with sat.-NaHCO3 and brine. The organic phase was dried over anh. Na2SO4 and concentrated in vacuo. The resulting crude was purified by CC using EtOAc/MeOH/NEt3 from 100/0/1 to 90/10/1 to yield 2.07 g of 2-fluoro-N-(3-{[2-((1S,2S)-6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydro-naphthalen-2-yl)-ethyl]-methyl-amino}-propyl)-N-(3-methoxy-2-methoxymethyl-2-methyl-propyl)-acetamide as orange oil.

Workup

  1. temperatureto warm up to rt for 1 h
  2. customquenched with sat.-NaHCO3
  3. dry with materialThe organic phase was dried over anh. Na2SO4
  4. concentrationconcentrated in vacuo
  5. dissolutionThe resulting crude ester was dissolved in EtOH (29 mL)
  6. additiontreated with 15 mL of a 1M NaOH solution
  7. stirringThe mixture was stirred for 15 min at rt
  8. concentrationconcentrated in vacuo
  9. washwashed with sat.-NaHCO3 and brine
  10. dry with materialThe organic phase was dried over anh. Na2SO4
  11. concentrationconcentrated in vacuo
  12. customThe resulting crude was purified by CC

Sources & evidence

ORD record
ord-1a99b5af91984b6c9f3f287c0966127c
Source dataset
uspto-grants-2013_05
Patent number
US08436205B2

Reaction notes

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