Dichloromethane → HCID 57705688, compound

HRID 2098919Notes

Reaction equation

HRID 2098919 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([CH2:16][OH:17])=[CH:12][C:11]=1[C@H:18]([OH:23])[C:19]([CH3:22])([CH3:21])[CH3:20].[F:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][C:26]=1[C:33]1[CH:38]=[CH:37][C:36]([CH2:39][OH:40])=[CH:35][C:34]=1[C@@H:41]([OH:46])[C:42]([CH3:45])([CH3:44])[CH3:43].C(Cl)Cl.[Si:50](Cl)([C:53]([CH3:56])([CH3:55])[CH3:54])([CH3:52])[CH3:51]>CN(C1C=CN=CC=1)C>[CH3:54][C:53]([Si:50]([CH3:52])([CH3:51])[O:17][CH2:16][C:13]1[CH:14]=[CH:15][C:10]([C:3]2[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=2[F:1])=[C:11]([C@@H:18]([OH:23])[C:19]([CH3:20])([CH3:22])[CH3:21])[CH:12]=1)([CH3:56])[CH3:55].[CH3:54][C:53]([Si:50]([CH3:52])([CH3:51])[O:40][CH2:39][C:36]1[CH:37]=[CH:38][C:33]([C:26]2[CH:27]=[C:28]([O:31][CH3:32])[CH:29]=[CH:30][C:25]=2[F:24])=[C:34]([C@H:41]([OH:46])[C:42]([CH3:43])([CH3:45])[CH3:44])[CH:35]=1)([CH3:56])[CH3:55]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 28928tert-Butyldimethylsilyl chlorideHCID 57706273HCID 57706273, compoundHCID 57706348HCID 57706348, compound

Product 2

HCID 57705688HCID 57705688, compoundHCID 57705810HCID 57705810, compound

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

To a stirred solution of (1R)-1-(2′-fluoro-4-(hydroxymethyl)-5′-(methyloxy)-1,1′-biphenyl-2-yl)-2,2-dimethyl-1-propanol or (1S)-1-(2′-fluoro-4-(hydroxymethyl)-5′-(methyloxy)-1,1′-biphenyl-2-yl)-2,2-dimethyl-1-propanol (T9.8 or T9.9) (0.300 g, 0.9 mmol) in DCM (10.00 mL, 155 mmol) at 23° C. was added tert-butyldimethylsilyl chloride (0.2 mL, 1 mmol), followed by TEA (0.2 mL, 1 mmol) and DMAP (0.01 g, 0.09 mmol). Stirring was continued for 16 hours. The mixture was then concentrated in vacuo to give the residue. The residue was purified by silica gel flash chromatography (0-10% EtOAc/hexane) to afford (1S)-1-(4-((((1,1-dimethylethyl)(dimethyl)silyl)oxy)methyl)-2′-fluoro-5′-(methyloxy)-1,1′-biphenyl-2-yl)-2,2-dimethyl-1-propanol or (1R)-1-(4-((((1,1-dimethylethyl)(dimethyl)silyl)oxy)methyl)-2′-fluoro-5′-(methyloxy)-1,1′-biphenyl-2-yl)-2,2-dimethyl-1-propanol T9.10 or T9.11 (0.375 g, 92% yield). MS ESI (pos.) m/e: 450.2 (M+H2O)+.

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. customto give the residue
  3. customThe residue was purified by silica gel flash chromatography (0-10% EtOAc/hexane)

Sources & evidence

ORD record
ord-3232d51dc7854e079438b315a860058a
Source dataset
uspto-grants-2013_05
Patent number
US08450522B2

Reaction notes

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